RESUMEN
INTRODUCTION: Cholestasis is the stoppage of bile flow, leading to the accumulation of potentially cytotoxic bile components in the liver. These cytotoxic molecules affect many organs. Cholestasis-induced lung injury is a severe complication that could lead to tissue fibrosis and respiratory distress. Substantial evidence indicates the role of oxidative stress and inflammatory response in the pathogenesis of cholestasis-associated pulmonary damage. Agmatine (AGM; 1-amino-4-guanidinobutane) is a biogenic amine endogenously synthesized in the human body. This amine provides potent anti-inflammatory and antioxidant properties. METHODS: In the current study, a series (six C57BL/6J male mice/group) of bile duct-ligated (BDL) animals were monitored at scheduled intervals (7, 14, and 28 days after the BDL operation) to ensure inflammatory response in their lung tissue (by analyzing their bronchoalveolar lavage fluid [BALF]). It was found that the level of inflammatory cells, pro-inflammatory cytokines, and IgG in the BALF reached their maximum level on day 28 after the BDL surgery. Therefore, other research groups were selected as follows: 1) Sham-operated (2.5 mL/kg normal saline, i.p., for 28 consecutive days), 2) BDL, 3) BDL + AGM (1 mg/kg/day, i.p., for 28 consecutive days), and 4) BDL + AGM (10 mg/kg/day, i.p., for 28 consecutive days). Then, the BALF was monitored at scheduled time intervals (7, 14, and 28 days post-BDL). RESULTS: It was found that pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), bile acids, bilirubin, and inflammatory cells (monocytes, neutrophils, and lymphocytes) were significantly increased in the BALF of BDL mice. Moreover, biomarkers of oxidative stress were significantly increased in the pulmonary tissue of cholestatic animals. Lung tissue histopathological changes, tissue collagen deposition, and increased TGF-ß were also detected. It was found that AGM significantly ameliorated cholestasis-induced lung injury. CONCLUSION: The effects of AGM on inflammatory indicators, oxidative stress biomarkers, and tissue fibrosis seem to play a pivotal role in its protective properties.
Asunto(s)
Agmatina , Colestasis , Lesión Pulmonar , Neumonía , Masculino , Ratones , Humanos , Animales , Agmatina/farmacología , Agmatina/uso terapéutico , Agmatina/metabolismo , Ratones Endogámicos C57BL , Colestasis/complicaciones , Colestasis/tratamiento farmacológico , Colestasis/metabolismo , Hígado , Estrés Oxidativo , Fibrosis , Neumonía/tratamiento farmacológico , Neumonía/prevención & control , Neumonía/complicaciones , Biomarcadores/metabolismo , Citocinas/metabolismo , Aminas Biogénicas/metabolismo , Aminas Biogénicas/farmacologíaRESUMEN
The current study was planned to assess the neuropharmacological benefits of the Cucurbita maxima seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris's water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that C. maxima exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of C. maxima may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, ß-carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of C. maxima seeds reduces the intensity of neurological problems like anxiety and depression.
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Ansiolíticos , Cucurbita , Animales , Depresión , Ansiedad , Antidepresivos , Ansiolíticos/farmacología , Aminas Biogénicas/farmacología , Conducta Animal , Aprendizaje por LaberintoRESUMEN
The effect of an edible film based on sage seed gum (SSG) incorporating 3 % Zataria multiflora Boiss essential oil (ZEO) was investigated on the storage quality and shelf life of tiger-tooth croaker (Otolithes ruber) fillets during storage at 4 ± 1 °C compared to the control film (SSG film without ZEO) and the Cellophane. The SSG-ZEO film significantly decelerated microbial growth (evaluated by total viable count, total psychrotrophic count, pH, TVBN) and lipid oxidation (evaluated by TBARS) compared to the others (P Ë 0.05). The antimicrobial activity of ZEO was the highest and the lowest on E. aerogenes (MIC: 0.196 µL/mL) and P. mirabilis (MIC: 0.977 µL/mL), respectively. E. aerogenes was identified as an indicator biogenic amine-producer in O. ruber fish at refrigerated temperature. The active film significantly lowered biogenic amine accumulation in the samples inoculated with E. aerogenes. A clear relationship was observed between the release of ZEO's phenolic compounds from the active film to the headspace and the reduction of microbial growth, lipid oxidation, and biogenic amine production in the samples. Consequently, SSG film containing 3 % ZEO is proposed as a biodegradable antimicrobial-antioxidant packaging to extend the shelf life and decrease the biogenic amine production in refrigerated seafood.
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Antiinfecciosos , Lamiaceae , Aceites Volátiles , Perciformes , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Bacterias , Embalaje de Alimentos , Lamiaceae/química , Antiinfecciosos/farmacología , Semillas , Aminas Biogénicas/farmacologíaRESUMEN
Postbiotics is a novel term proposed to describe as a set of bioactive compounds obtained from beneficial microorganisms. In this work, postbiotics from four lactic acid bacteria (LAB) including Leuconostoc mesenteroides subsp. cremoris, Pediococcus acidilactici, Lactococcus lactis subsp. lactis and Streptococcus thermophilus were prepared in MRS broth. The antimicrobial properties and organic acids content of postbiotics were also investigated. Postbiotics were used to tentatively reduce the production of biogenic amines by foodborne pathogens (i.e., Salmonella paratyphi A and Escherichia coli) on lysine decarboxylase broth (LDB). Experimental data showed that acetic, propionic, and butyric acids were in the range of 387.51-709.21 mg/L, 0.00-1.28 mg/L, and 0.00-20.98 mg/L, respectively. The inhibition zone of postbiotics on E. coli and S. paratyphi A were 11.67, and 12.33 mm, respectively. Two different levels of postbiotics (25%, and 50%) were used in LDB to measure the diamines (cadaverine and putrescine), polyamines (agmatine, spermidine, and spermine, ammonia), and other biogenic amine formation by pathogens. E. coli produced cadaverine and putrescine with concentrations of 1072.21 and 1114.18 mg/L, respectively. The postbiotics reduced cadaverine formation by 67% in E. coli, and cadaverine production was mostly suppressed by postbiotics from P. acidilactici in E. coli (97%) and L. lactis subsp. lactis in S. paratyphi A (90%). Putrescine production by E. coli was reduced by 94% with postbiotics of P. acidilactici at a concentration of 25%, whereas putrescine production by S. paratyphi A has been decreased by 61% in the presence of postbiotics from L. lactis subsp. Lactis with a 25% concentration. The results revealed that an increase in postbiotics concentration (from 25% to 50%) in LDB may lead to synergistic effects, resulting from the production of biogenic amines by microbial pathogens. It was importantly concluded that postbiotics of LAB may degrade biogenic amines or prevent their formation by foodborne pathogens.
Asunto(s)
Agmatina , Carboxiliasas , Lactococcus lactis , Agmatina/metabolismo , Agmatina/farmacología , Amoníaco/metabolismo , Aminas Biogénicas/metabolismo , Aminas Biogénicas/farmacología , Butiratos/metabolismo , Cadaverina/metabolismo , Carboxiliasas/metabolismo , Escherichia coli/metabolismo , Lactococcus lactis/metabolismo , Lisina/metabolismo , Putrescina/metabolismo , Espermidina/metabolismo , Espermidina/farmacología , Espermina/metabolismo , Espermina/farmacologíaRESUMEN
Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1ß, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.
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Aminas Biogénicas/farmacología , Inmunomodulación/efectos de los fármacos , Quinurenina/análogos & derivados , Animales , Aminas Biogénicas/metabolismo , Aminas Biogénicas/uso terapéutico , Línea Celular Tumoral , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Células Endoteliales , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Inflamación , Interferón gamma/farmacología , Quinurenina/metabolismo , Quinurenina/farmacología , Quinurenina/uso terapéutico , Ratones , FN-kappa B/metabolismo , Nefritis/tratamiento farmacológico , Nefritis/inmunología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Triptófano/metabolismoRESUMEN
The effects of three biogenic amines (DA, NE and 5-HT) on the immune signaling pathway and immune response of hemocytes in shrimp were investigated through in vitro experiments. The results showed that the G protein effectors (AC, PLC), the second messengers (cAMP, DAG), Calmodulin (CaM) and protein kinases (PKA, PKC) of DA and NE groups shared a similar trend in which all intracellular signaling factors increased significantly and reached the maximum at 3 h. The concentrations of AC, cAMP and PKA in 5-HT groups decreased significantly compared with the control group, while the concentrations of PLC, CaM, DAG and PKC in 5-HT groups increased markedly. The immune parameters such as total hemocyte count (THC), cell viability, antibacterial activity and bacteriolytic activity, as well as prophenoloxidase (proPO) activity in three biogenic amines groups decreased significantly, while the phenoloxidase (PO) activity increased significantly. The phagocytic activity in DA and NE groups decreased significantly, while that in 5-HT groups increased markedly and reached the highest level at 1 h. Among these three biogenic amines, DA showed the strongest effect on the immune activity of the hemocytes, whereas 5-HT had the least effect. In addition, we speculated that DA and NE might regulate phagocytosis by activating intracellular AC-cAMP-PKA pathway while 5-HT might inhibit intracellular AC-cAMP-PKA pathway. Moreover, the activation of proPO system might be related to PLC-DAG-PKC and PLC-CaM pathway.
Asunto(s)
Aminas Biogénicas/farmacología , Hemocitos/efectos de los fármacos , Hemocitos/inmunología , Fenómenos del Sistema Inmunológico/efectos de los fármacos , Penaeidae/efectos de los fármacos , Penaeidae/inmunología , Animales , Proteínas de Artrópodos/metabolismo , Calmodulina/metabolismo , Catecol Oxidasa/metabolismo , Precursores Enzimáticos/metabolismo , Proteínas de Unión al GTP/metabolismo , Hemocitos/metabolismo , Penaeidae/metabolismo , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Proteínas Quinasas/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: During blood feeding, sand flies inoculate salivary proteins that interact with the host haemostatic system. The blocking of biogenic amines such as serotonin and histamine helps to limit vasodilatation and clot formation, and thus enables the insect to finish the blood-feeding process. In sand flies, an amine-binding ability is known only for the yellow-related proteins of Phlebotomus and Lutzomyia vectors, but not yet for members of the genus Sergentomyia. METHODS: The ability of Phlebotomus argentipes and Sergentomyia schwetzi recombinant yellow-related salivary proteins to bind histamine and serotonin was measured by microscale thermophoresis. Both sand fly species were also fed through a chicken-skin membrane on blood mixed with histamine or serotonin in order to check the effects of biogenic amines on sand fly fitness. Additionally, fecundity and mortality were compared in two groups of P. argentipes females fed on repeatedly-bitten and naive hamsters, respectively. RESULTS: The P. argentipes recombinant yellow-related protein PagSP04 showed high binding affinity to serotonin and low affinity to histamine. No binding activity was detected for two yellow-related proteins of S. schwetzi. Elevated concentrations of serotonin significantly reduced the amount of eggs laid by P. argentipes when compared to the control. The fecundity of S. schwetzi and the mortality of both sand fly species were not impaired after the experimental membrane feeding. Additionally, there were no differences in oviposition or mortality between P. argentipes females fed on immunized or naive hamsters. CONCLUSIONS: Our results suggest that in natural conditions sand flies are able to cope with biogenic amines or anti-saliva antibodies without any influence on their fitness. The serotonin binding by salivary yellow-related proteins may play an important role in Phlebotomus species feeding on mammalian hosts, but not in S. schwetzi, which is adapted to reptiles.
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Aminas Biogénicas , Psychodidae/metabolismo , Proteínas y Péptidos Salivales , Animales , Anticuerpos , Aminas Biogénicas/sangre , Aminas Biogénicas/farmacología , Sangre/metabolismo , Cricetinae , Evolución Molecular , Fertilidad/efectos de los fármacos , Histamina/sangre , Mordeduras y Picaduras de Insectos/inmunología , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Mamíferos , Mortalidad , Phlebotomus/metabolismo , Unión Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reptiles , Saliva/inmunología , Proteínas y Péptidos Salivales/química , Proteínas y Péptidos Salivales/metabolismo , Serotonina/sangreRESUMEN
Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors (GPCRs) that are evolutionarily conserved in vertebrates. The first discovered TAAR1 is mainly expressed in the brain, and is able to detect low abundant trace amines. TAAR1 is also activated by several synthetic compounds and psychostimulant drugs like amphetamine. Activation of TAAR1 by specific agonists can regulate the classical monoaminergic systems in the brain. Further studies have revealed that other TAAR family members are highly expressed in the olfactory system which are termed olfactory TAARs. In vertebrates, olfactory TAARs can specifically recognize volatile or water-soluble amines. Some of these TAAR agonists are produced by decarboxylation of amino acids. In addition, some TAAR agonists are ethological odors that mediate animal innate behaviors. In this study, we provide a comprehensive review of TAAR agonists, including their structures, biosynthesis pathways, and functions.
Asunto(s)
Aminas Biogénicas/metabolismo , Estimulantes del Sistema Nervioso Central/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Animales , Aminas Biogénicas/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Humanos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
In the present study, screening of a library of 49,087 compounds at the excitatory amino acid transporter subtype 3 (EAAT3) led to the identification of 2-(furan-2-yl)-8-methyl-N-(o-tolyl)imidazo[1,2-a]pyridin-3-amine (3a) which showed a >20-fold preference for inhibition of EAAT3 (IC50 = 13 µM) over EAAT1,2,4 (EAAT1: IC50 â¼ 250 µM; EAAT2,4: IC50 > 250 µM). It was shown that a small lipophilic substituent (methyl or bromine) at the 7- and/or 8-position was essential for activity. Furthermore, the substitution pattern of the o-tolyl group (compound 5b) and the chemical nature of the substituent in the 2-position (compound 7b) were shown to be essential for the selectivity toward EAAT3 over EAAT1,2. The most prominent analogues to come out of this study are 3a and 3e that display â¼35-fold selectivity for EAAT3 (IC50 = 7.2 µM) over EAAT1,2,4 (IC50 â¼ 250 µM).
Asunto(s)
Transportador 3 de Aminoácidos Excitadores/antagonistas & inhibidores , Piridinas/química , Piridinas/farmacología , Aminas Biogénicas/química , Aminas Biogénicas/farmacología , Cromatografía en Capa Delgada/métodos , Relación Dosis-Respuesta a Droga , Transportador 3 de Aminoácidos Excitadores/metabolismo , Células HEK293 , Humanos , Relación Estructura-ActividadRESUMEN
Methylmercury (MeHg) is an environmental toxicant with detrimental effects on the developing brain and adult nervous system. The main mechanisms identified include oxidative stress, changes in intracellular calcium, mitochondrial changes, inhibition of glutamate uptake, of protein synthesis and disruption of microtubules. However, little is known about mechanisms of protection against MeHg neurotoxicity. We found that resveratrol (10 µM) and ascorbic acid (200 µM) protected MeHg-induced cell death in primary cultures of cortical neurons. In this work, we aimed at finding additional targets that may be related to MeHg mode of action in cell toxicity with special emphasis in cell protection. We wonder whether neurotransmitters may affect the MeHg effects on neuronal death. Our findings show that neurons exposed to low MeHg concentrations exhibit less mortality if co-exposed to 10 µM dopamine (DA). However, DA metabolites, HVA (homovanillic acid) and DOPAC (3,4-dihydroxyphenylacetic acid) are not responsible for such protection. Furthermore, both DA D1 and D2 receptors agonists showed a protective effect against MeHg toxicity. It is striking though that DA receptor antagonists SKF83566 (10 µM) and haloperidol (10 µM) did not inhibit DA protection against MeHg. In addition, the protective effect of 10 µM DA against MeHg-induced toxicity was not affected by additional organochlorine pollutants exposure. Our results also demonstrate that cells exposed to MeHg in presence of 100 µM acetylcholine (ACh), show an increase in cell mortality at the "threshold value" of 100 nM MeHg. Finally, norepinephrine (10 µM) and serotonin (20 µM) also had an effect on cell protection. Altogether, we propose to further investigate the additional mechanisms that may be playing an important role in MeHg-induced cytotoxicity.
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Antioxidantes/farmacología , Corteza Cerebral/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Neuronas/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Aminas Biogénicas/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Citotoxinas/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Neuronas/metabolismo , Neuronas/patología , Neuroprotección/fisiología , Neurotransmisores/farmacología , Estrés Oxidativo/fisiología , EmbarazoRESUMEN
For more than a century, visual learning and memory have been studied in the honeybee Apis mellifera using operant appetitive conditioning. Although honeybees show impressive visual learning capacities in this well-established protocol, operant training of free-flying animals cannot be combined with invasive protocols for studying the neurobiological basis of visual learning. In view of this, different attempts have been made to develop new classical conditioning protocols for studying visual learning in harnessed honeybees, though learning performance remains considerably poorer than that for free-flying animals. Here, we investigated the ability of honeybees to use visual information acquired during classical conditioning in a new operant context. We performed differential visual conditioning of the proboscis extension reflex (PER) followed by visual orientation tests in a Y-maze. Classical conditioning and Y-maze retention tests were performed using the same pair of perceptually isoluminant chromatic stimuli, to avoid the influence of phototaxis during free-flying orientation. Visual discrimination transfer was clearly observed, with pre-trained honeybees significantly orienting their flights towards the former positive conditioned stimulus (CS+), thus showing that visual memories acquired by honeybees are resistant to context changes between conditioning and the retention test. We combined this visual discrimination approach with selective pharmacological injections to evaluate the effect of dopamine and octopamine in appetitive visual learning. Both octopaminergic and dopaminergic antagonists impaired visual discrimination performance, suggesting that both these biogenic amines modulate appetitive visual learning in honeybees. Our study brings new insight into cognitive and neurobiological mechanisms underlying visual learning in honeybees.
Asunto(s)
Abejas/efectos de los fármacos , Aminas Biogénicas/farmacología , Dopamina/farmacología , Octopamina/farmacología , Percepción Visual , Animales , Abejas/fisiología , Aminas Biogénicas/administración & dosificación , Condicionamiento Operante , Aprendizaje Discriminativo , Dopamina/administración & dosificación , Memoria , Octopamina/administración & dosificaciónRESUMEN
Foodborne pathogens (FBP) represent an important threat to the consumers' health as they are able to cause different foodborne diseases. In order to eliminate the potential risk of those pathogens, lactic acid bacteria (LAB) have received a great attention in the food biotechnology sector since they play an essential function to prevent bacterial growth and reduce the biogenic amines (BAs) formation. The foodborne illnesses (diarrhea, vomiting, and abdominal pain, etc.) caused by those microbial pathogens is due to various reasons, one of them is related to the decarboxylation of available amino acids that lead to BAs production. The formation of BAs by pathogens in foods can cause the deterioration of their nutritional and sensory qualities. BAs formation can also have toxicological impacts and lead to different types of intoxications. The growth of FBP and their BAs production should be monitored and prevented to avoid such problems. LAB is capable of improving food safety by preventing foods spoilage and extending their shelf-life. LAB are utilized by the food industries to produce fermented products with their antibacterial effects as bio-preservative agents to extent their storage period and preserve their nutritive and gustative characteristics. Besides their contribution to the flavor for fermented foods, LAB secretes various antimicrobial substances including organic acids, hydrogen peroxide, and bacteriocins. Consequently, in this paper, the impact of LAB on the growth of FBP and their BAs formation in food has been reviewed extensively.
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Aminas Biogénicas/metabolismo , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Lactobacillales/fisiología , Aminas Biogénicas/farmacología , Inocuidad de los Alimentos , HumanosRESUMEN
Indolealkylamines (IAAs) are biogenic amines and derivatives of 5-hydroxytryptamine, acting primarily on serotonin receptors. IAAs are often considered the most thoroughly investigated group of aromatic amines in the amphibian skin. On the contrary, at present the detailed knowledge of these compounds in lower organisms is still limited and the biogenic amine receptors, mediating hormonal and modulatory functions, are largely unknown in primitive invertebrates. However, some active research is currently underway investigating this class of biogenic amines. Notably, during the last three decades several investigations have demonstrated the biological activity of endogenous biogenic amines in cnidarians, which are known to be the lowest beings equipped with an effective, even though rudimentary, nervous system. Toads, especially those from the Bufonidae family, constitute a significant part of the amphibian family and are an identified source of IAAs. To date fourteen IAAs have been identified in the skins of toad species. All are 5-substituted IAA derivatives acting mainly on the central nervous system (CNS), with most exhibiting some degrees of 5-HT2A receptor selectivity. This selective ability presents potential for their use in the development of treatments for various disorders such as schizophrenia, depression, anxiety, obsessive-compulsive disorders and chronic pain conditions. There are indications that some IAAs may also show subclass selectivity through binding to multiple 5-HT receptor subtypes. Thus, there exists an additional promising platform for the development of therapeutics targeting multiple 5-HT receptors. In this review, IAAs occurring naturally in various species of toad skins, which have been identified and isolated since 1944 are summarized and comparisons are made with similar biogenic amines recognized in cnidarians to date. Such comparisons highlight the potential to utilize existing knowledge gathered from vertebrates, such as toads in order to improve the understanding of the activities of such compounds in lower invertebrates.
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Anuros , Aminas Biogénicas/aislamiento & purificación , Aminas Biogénicas/farmacología , Sistema Nervioso Central/efectos de los fármacos , Cnidarios , Animales , Aminas Biogénicas/química , Humanos , Indoles/química , Indoles/aislamiento & purificación , Indoles/farmacología , Invertebrados , Piel/química , VertebradosRESUMEN
Rice produces a wide array of phytoalexins in response to pathogen attacks and UV-irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from UV-treated rice leaves showed that several phenolic compounds in addition to sakuranetin accumulated remarkably in rice leaves. We isolated two compounds from UV-treated rice leaves using silica gel column chromatography and preparative HPLC. The isolated phenolic compounds were identified as phenylamide compounds: N-trans-cinnamoyltryptamine and N-p-coumaroylserotonin. Expression analysis of biosynthetic genes demonstrated that genes for arylamine biosynthesis were upregulated by UV irradiation. This result suggested that phenylamide biosynthetic pathways are activated in rice leaves by UV treatment. To unravel the role of UV-induced phenylamides as phytoalexins, we examined their antimicrobial activity against rice fungal and bacterial pathogens. N-trans-Cinnamoyltryptamine inhibited the growth of rice brown spot fungus (Bipolaris oryzae). In addition to the known antifungal activity to the blast fungus, sakuranetin had antimicrobial activity toward B. oryzae and Rhizoctonia solani (rice sheath blight fungus). UV-induced phenylamides and sakuranetin also had antimicrobial activity against rice bacterial pathogens for grain rot (Burkholderia glumae), blight (Xanthomonas oryzae pv. oryzae) and leaf streak (X. oryzae pv. oryzicola) diseases. These findings suggested that the UV-induced phenylamides in rice are phytoalexins against a diverse array of pathogens.
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Antiinfecciosos , Ascomicetos/crecimiento & desarrollo , Aminas Biogénicas , Burkholderia/crecimiento & desarrollo , Hojas de la Planta , Rhizoctonia/crecimiento & desarrollo , Rayos Ultravioleta , Xanthomonas/crecimiento & desarrollo , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/metabolismo , Antiinfecciosos/farmacología , Aminas Biogénicas/biosíntesis , Aminas Biogénicas/química , Aminas Biogénicas/aislamiento & purificación , Aminas Biogénicas/farmacología , Regulación de la Expresión Génica , Oryza/química , Oryza/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismoRESUMEN
BACKGROUND: Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages. METHODS: Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM) and mast cells staining were evaluated. RESULTS: PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages. CONCLUSION: PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.
Asunto(s)
Envejecimiento/inmunología , Pulmón/citología , Pulmón/fisiología , Ovinos , Alérgenos/farmacología , Animales , Animales Recién Nacidos , Aminas Biogénicas/farmacología , Broncoconstricción/efectos de los fármacos , Cimetidina/farmacología , Histamina/farmacología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Supervivencia TisularRESUMEN
The Maillard reaction of sugars and amines resulting in the formation of glycosylamines and Amadori products is of biological significance, for drug delivery, role in central nervous system, and other potential applications. We have examined the interaction of (18) F-fluorodeoxyglucose ((18) F-FDG) with biological amines to study the formation of (18) F-fluorodeoxyglycosylamines ((18) F-FDGly). Respective amines N-allyl-2-aminomethylpyrrolidine (NAP) and 2-(4'-aminophenyl)-6-hydroxybenzothiazole (PIB precursor) were mixed with FDG to provide glycosylamines, FDGNAP and FDGBTA. Radiosynthesis using (18) F-FDG (2-5 mCi) was carried out to provide (18) F-FDGNAP and (18) F-FDGBTA. Binding of FDGBTA and (18) F-FDGBTA was evaluated in human brain sections of Alzheimer's disease (AD) patients and control subjects using autoradiography. Both FDGNAP and FDGBTA were isolated as stable products. Kinetics of (18) F-FDGNAP reaction indicated a significant product at 4 h (63% radiochemical yield). (18) F-FDGBTA was prepared in 57% yield. Preliminary studies of FDGBTA showed displacement of (3) H-PIB (reduced by 80%), and (18) F-FDGBTA indicated selective binding to Aß-amyloid plaques present in postmortem AD human brain, with a gray matter ratio of 3 between the AD patients and control subjects. We have demonstrated that (18) F-FDG couples with amines under mild conditions to form (18) F-FDGly in a manner similar to click chemistry. Although these amine derivatives are stable in vitro, stability in vivo and selective binding is under investigation.
Asunto(s)
Benzotiazoles/química , Aminas Biogénicas/síntesis química , Fluorodesoxiglucosa F18/química , Reacción de Maillard , Pirrolidinas/química , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/metabolismo , Aminas Biogénicas/farmacología , Estudios de Casos y Controles , Humanos , Unión Proteica , CintigrafíaRESUMEN
Using pairings of male crayfish Procambarus clarkii with a 3-7% difference in size, we confirmed that physically larger crayfish were more likely to win encounters (winning probability of over 80%). Despite a physical disadvantage, small winners of the first pairings were more likely to win their subsequent conflicts with larger naive animals (winning probability was about 70%). By contrast, the losers of the first pairings rarely won their subsequent conflicts with smaller naive animals (winning probability of 6%). These winner and loser effects were mimicked by injection of serotonin and octopamine. Serotonin-injected naive small crayfish were more likely to win in pairings with untreated larger naive crayfish (winning probability of over 60%), while octopamine-injected naive large animals were beaten by untreated smaller naive animals (winning probability of 20%). Furthermore, the winner effects of dominant crayfish were cancelled by the injection of mianserin, an antagonist of serotonin receptors and were reinforced by the injection of fluoxetin, serotonin reuptake inhibitor, just after the establishment of social order of the first pairings. Injection of octopamine channel blockers, phentolamine and epinastine, by contrast, cancelled the loser effects. These results strongly suggested that serotonin and octopamine were responsible for winner and loser effects, respectively.
Asunto(s)
Conducta Agonística/efectos de los fármacos , Astacoidea/efectos de los fármacos , Astacoidea/fisiología , Aminas Biogénicas/farmacología , Predominio Social , Animales , Astacoidea/anatomía & histología , Conducta Animal/efectos de los fármacos , Aminas Biogénicas/administración & dosificación , Tamaño Corporal , Inyecciones , Masculino , Mianserina/farmacología , Octopamina/administración & dosificación , Octopamina/farmacología , Fentolamina/administración & dosificación , Fentolamina/farmacología , Serotonina/administración & dosificación , Serotonina/farmacologíaRESUMEN
In smooth muscles of mollusc Anodonta cygnea, hormones produce regulatory effects on the adenylyl cyclase (AC) signaling system via receptors of the serpentine (biogenic amine, isoproterenol, glucagon) and of tyrosine kinase (insulin) types. Intracellular mechanisms of their action are interconnected. Use of hormones, their antagonists, and pertussis toxin at the combined action of insulin and biogenic amines or of glucagon on the AC activity allows revealing possible intersection points in mechanisms of their action. The combined effect of insulin and serotonin or of glucagon leads to a decrease of stimulation of AC by these hormones, whereas at action of insulin and isoproterenol the AC-stimulatory effect of insulin is blocked, while the AC-inhibitory effect of isoproterenol is preserved both in the presence and in the absence of the non-hydrolyzed GTP analog - guanylylimidodiphosphate (GppNHp). Specific blocking of the AC-stimulatory serotonin effect by cyproheptadine - an antagonist of serotonin receptors - did not affect stimulation of AC by insulin. Beta-adrenoblockers (propranolol and alprenolol) interfered with inhibition of the AC activity by isoproterenol, but did not change the AC stimulation by insulin. Pertussis toxin blocked the AC-inhibitory effect of isoproterenol and attenuated the AC-stimulatory effect of insulin. Thus, in muscles of the mollusc Anodonta cygnea there have been revealed negative interrelations between the AC system, which are realized at the combined effect of insulin and serotonin or of glucagon, probably at the level of receptor of the serpentine type (serotonin, glucagon), while at action of insulin and isoproterenol - at the level of interaction of G1 protein and AC.
Asunto(s)
Adenilil Ciclasas/metabolismo , Anodonta/efectos de los fármacos , Aminas Biogénicas/farmacología , Glucagón/farmacología , Insulina/farmacología , Transducción de Señal/efectos de los fármacos , Inhibidores de Adenilato Ciclasa , Antagonistas Adrenérgicos beta/farmacología , Animales , Anodonta/enzimología , Anodonta/fisiología , Aminas Biogénicas/administración & dosificación , Aminas Biogénicas/fisiología , Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Interacciones Farmacológicas , Glucagón/administración & dosificación , Glucagón/fisiología , Técnicas In Vitro , Insulina/administración & dosificación , Insulina/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/enzimología , Músculo Liso/fisiología , Transducción de Señal/fisiologíaRESUMEN
Certain biogenic amines, such as 2-PEA, TYR, or T1AM, modulate blood pressure, cardiac function, brain monoaminergic systems, and olfaction-guided behavior by specifically interacting with members of a group of rhodopsin-like receptors, TAAR. A receptor that is absent from olfactory epithelia but had long been identified in the brain and a variety of peripheral tissues, TAAR1 has been found recently in blood B cells, suggesting a functional role of TAAR1 in these cells. With the present study, we have set out to clarify the expression and functional roles of TAAR in different isolated human blood leukocyte types. Here, we report the functional expression of TAAR1 and its closest relative TAAR2 in blood PMN and T and B cells. Both receptors are coexpressed in a subpopulation of PMN, where they are necessary for the chemosensory migration toward the TAAR1 ligands 2-PEA, TYR, and T1AM, with EC50 values of 0.43 ± 0.05 nM, 0.52 ± 0.05 nM, and 0.25 ± 0.04 nM, respectively. The same amines, with similar potencies, triggered cytokine or Ig secretion, in purified blood T or B cells, respectively. Notably, 2-PEA regulated mRNA expression of 28 T cell function-related genes, above all of the CCL5. In siRNA-guided experiments, TAAR1 and TAAR2 proved to be necessary for amine-induced blood leukocyte functions. In summary, our results demonstrate that biogenic amines potently regulate blood cell functions via TAAR1 and TAAR2 and open the perspective of their specific pharmacological modulation.
Asunto(s)
Aminas Biogénicas/farmacología , Leucocitos Mononucleares/inmunología , Receptores Acoplados a Proteínas G/inmunología , Anticuerpos/inmunología , Aminas Biogénicas/inmunología , Quimiocina CCL5/inmunología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucocitos Mononucleares/citología , MasculinoRESUMEN
In invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates. The α- and ß-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine. Similarly, the Tyramine 1 subgroup of receptors (or Octopamine/Tyramine receptors) are better activated by tyramine than octopamine. However, recently, a new Tyramine 2 subgroup of receptors was identified, which appears to be activated highly preferentially by tyramine. We examined immunocytochemically the ability of CG7431, the founding member of this subgroup from Drosophila melanogaster, to be internalized in transfected Chinese hamster ovary (CHO) cells by different agonists. It was only internalized after activation by tyramine. Conversely, the structurally related receptor, CG16766, was internalized by a number of biogenic amines, including octopamine, dopamine, noradrenaline, adrenaline, which also were able to elevate cyclic AMP levels. Studies with synthetic agonists and antagonists confirm that CG16766 has a different pharmacological profile to that of CG7431. Species orthologues of CG16766 were only found in Drosophila species, whereas orthologues of CG7431 could be identified in the genomes of a number of insect species. We propose that CG16766 represents a new group of tyramine receptors, which we have designated the Tyramine 3 receptors.