Systemic injection of an H4 receptor agonist induces a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex in mice

Studies have shown that an injection with the histamine H4 receptor agonist VUF-8430 modulates emotional memory processes. In the present study, the aim was to verify if intraperitoneal (ip) injection of VUF-8430 (500 ng/kg) in mice affects the synthesis of proteins required for memory consolidation processes by activating the phosphorylation of CREB (pCREB) in classical structures linked to emotional memory (prefrontal cortex, amygdala, and hippocampus) and the cerebellar vermis, a structure that has also been recently implicated in emotional memory. The results obtained using western blot analysis demonstrated that VUF-8430 induced a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex, suggesting that this dose impaired the activation of cell signaling pathways in these structures. There was no change in protein expression in the amygdala and hippocampus. Our results are preliminary, and further investigations are needed to investigate the role of the H4 receptors in the central nervous system.

Antihistamínicos Parte II - ¿Cuáles son las opciones y en qué basarse para elegir la mejor? / Antihistamines Part II - What are the options and how to choose the best?

Los antihistamínicos han sido usados durante los últimos 50 años y se han convertido en los medicamentos de mayor prescripción en el mundo. En este artículo se revisa el desarrollo de nuestro conocimiento referente a la histamina en el transcurso del siglo, como mediador biológico almacenado y liberado mayormente por los basófilos y mastocitos; mediador biológico situado en diferentes tejidos corporales, y otras células, con un papel fisiológico fundamental en el control de la secreción de ácido gástrico y un papel fisiopatológico en una gama de trastornos alérgicos. La síntesis y estudios farmacológicos de agonistas y antagonistas selectivos han establecido la existencia de cuatro tipos de receptores de histamina y antagonistas de ellos, que han encontrado muy importantes aplicaciones terapéuticas. Debido al aumento de la prevalencia de las enfermedades alérgicas según el Libro Blanco de Alergia (WAO), se deben crear normas que promuevan el uso de los antihistamínicos de manera adecuada y racional. De esta manera, la correcta elección debe ser realizada de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones particulares en pacientes con algún riesgo incrementado. El crear normas que promuevan una práctica terapéutica óptima o uso racional de dichos medicamentos. Elegirlos de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones especiales en pacientes portadores de ciertas enfermedades de riesgo a utilizarlos.(AU)

Antihistamines have been used for the past 50 years and have become the most prescribed drugs in the world. This article reviews the development of our knowledge concerning the histamine in the course of the century, as a biological mediator mostly stored and released by basophils and mast cells biological mediator located in different body tissues, and other cells, having a fundamental physiological role in the control of gastric acid secretion and pathophysiological role in a variety of allergic disorders. The synthesis and pharmacological studies of selective agonists and antagonists has established the existence of four types of histamine receptor antagonists and histamine receptor found important therapeutic applications. Power demonstrations relate most allergic diseases whose symptoms are chronic and persistent emphasis by (WAO) White Paper on Alergia1 a steady increase in allergic diseases with a prevalence of 30-40% of the world population affected at least one allergic condition, considering the most common allergic rhinitis and chronic diseases common in our modern society. Creating standards that promote optimal therapeutic practice or rational use of such drugs. Choose them according to their efficacy, tolerability, safety, age group, situations and special precautions in patients with certain diseases risk to use. (AU)

Histamina, receptores de histamina e anti-histamínicos: novos conceitos / Histamine, histamine receptors and antihistamines: new concepts

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.

Drugs with antihistamine action are the most commonly prescribed medication in daily dermatologic practice, both to adults and children. This article addresses new concepts of the role of histamine receptors (H1 receptors) and discusses the anti-inflammatory effects of these drugs. Second generation antihistamines differs from first generation because of their high specificity and affinity for peripheral H1-receptors. Second generation antihistamines are also less likely to produce sedation because they have less effect on the central nervous system. Although the efficacy of the various H1-antihistamines in the treatment of allergic patients is similar, even when comparing first- and second-generation drugs, these drugs are still very different in terms of their chemical structure, pharmacology and toxic properties. Consequently, knowledge of their pharmacokinetic and pharmacodynamic characteristics is essential for a better medical care, especially that offered to pregnant women, children, the elderly, and patients with comorbidities.

Histamine and spontaneously released mast cell granules ffect the cell growth of human hepatocellular carcinoma cells

The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H1 and H2 and that the selective H1 antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H2 antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of beta-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and beta-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth.

Influence of histamine and H1-receptor antagonists on ejaculated human spermatozoa: role of intrasperm Ca2+.

Histamine reduced sperm viability in a dose- and time-dependent manner, accompanied by rise in intrasperm Ca2+. Further, 2',4'-dichlorobenzamil hydrochloride (DBZ), a Na+-Ca2+ exchange inhibitor, known to elevate intrasperm Ca2+, potentiated both, elevation of intrasperm Ca2+ and spermicidal action of histamine. Pretreatment of sperm with very low doses of H1-receptor antagonists (chlorpheniramine, promethazine or diphenhydramine) prevented the histamine-induced elevation of intrasperm Ca2+ as well as its spermicidal action. However, pretreatment with famotidine, a H2-receptor antagonist did not produce such a protective action. The results strongly suggest that histamine elicits its spermicidal action via H1-receptors present on sperm cells.

Midriasis farmacológica en conejos inducida por antagonistas de histamina / Pharmacologic midriasis induced by histamine antagonist in rabits

El propósito de este trabajo es determinar el efecto de antagonistas de histamina sobre el esfínter pupilar y la superficie ocular en conejos pigmentados. Para ello se realizó un estudio experimental, longitudinal y comparativo. Se estudiaron 50 ojos de 25 conejos, divididos en 4 grupos: I cimetidina, II clorfenamina, III tropicamida al 1 por ciento y IV fenilefrina al 10 por ciento + ciclopentolato al 1 por ciento. Como resultado, se demostró que la combinación de cimetidina y tropicamida al 1 por ciento produce pérdida de reflejo pupilar a los 5 minutos, midriasisi máxima a los 15 minutos, delcinando a los 45 minutos de su aplicacion. Se concluye que la combinación de cimetidina y tropicamida al 1 por ciento en forma tópica, induce pérdida del reflejo pupilar y midriasis a corto plazo desapareciendo rápidamente el afecto

Central serotonergic and histaminergic modulation of peripheral inflammation and nociception in rats.

Possible central serotonergic and histaminergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced acute pedal inflammation as an experimental model. Intracerebroventricular (icv) administration of central inhibitory neurotransmitter, serotonin and its precursor, 5-hydroxytryptophan (5-HTP) attenuated the oedema volume and exudate protein content alongwith augmentation in pain threshold. On the contrary, cyproheptadine, a 5-HT-receptor antagonist and selective serotonin synthesis inhibitor, parachlorophenylalanine (PCPA) produced oedema augmenting and pro-nociceptive effects besides elevating the protein content of the exudate. Centrally administered histamine attenuated pedal oedema, nociception as well as protein concentration in oedema fluid. Cimetidine, an H2 histaminergic receptor blocker did not produce any significant effect on inflammation.

Effects of antihistamines on wound healing.

Role of antihistamines (H1 and H2 blockers) in wound healing by utilizing incision and dead space wound models in albino rats was investigated. H1 blockers (mepyramine and promethazine) were found to decrease breaking strength of 10 day old dermal incision wounds and collagen content (as hydroxyproline) and breaking strength of granulation tissue harvested over tubular implant. On the other hand H2 blockers (Cimetidine and ranitidine) did not alter the above parameters. The findings that H1 blockers suppress healing implicate H1 receptors in alleged prohealing effect of histamine, and suggest clinical evaluation of these agents for suppression of overhealing states like keloid, adhesions and strictures.

Histaminergic mechanisms in experimental convulsions.

Effect of some histamine (HA) agonists and antagonists were assessed on electroshock (MES) convulsions in mice and rats. In mice, pretreatment with the HA precursor, l-histidine (100, 500 and 1000 mg/kg) precipitated seizures after a subthreshold (30 mA) stimulus. Both incidence (%) and tonic hind limb extensor phase (THE) were more than that in vehicle treated controls. The H1 blockers, pheniramine (25 mg/kg) and promethazine (25 mg/kg) both protected against (60 mA) MES and both incidence of convulsions and THE were reduced. A similar protective effect was not seen with either the H2 blocker, cimetidine (up to 200 mg/kg), or atropine (1 mg/kg). In rats, both the classical antihistamines blocked MES seizures, whereas, the H2-blocker, cimetidine, and atropine were, ineffective. Further, both H1 blockers were ineffective in antagonizing seizures induced by pentylenetetrazole, INH, caffeine or strychnine. These results are discussed in light of a possible HA-ergic regulation of experimental convulsions.

Effects of calcium and EDTA on rat skin capillary permeability and on its response to histamine, serotonin and bradykinin

Para estudiar los efectos del calcio y el EDTA sobre la permeabilidad vascular y su respuesta a mediadores de la inflamación se utilizó el método de la extravasación del azul de Evans. El Ca2+ provocó una disminución concentración-dependeniente de la permeabilidad capilar. El EDTA en concentraciones 0.2 mM o mayores tuvo el efecto opuesto. La extravasación provocada por la inyección intradérmica de histamina 100 microng/ml, serotoninas 5 microng/ml y bradiquinina 5 microng/ml, fue menor cuando se innyectó en el mismo sitio Ca2+ 8mM y mayor en presencia de EDTA e mM. Los efectos del EDTA fueron inhibidos por el calcio. Estos resultados sugieren que, en la piel de la rata, el calcio disminuye la permeabilidad capilar y su respuesta a histamina, serotonina y bradiquinina

Inhibición por terfenadina de la respuesta cutánea histamínica / Inhibition by terfenadine of the cutaneous histamine response

Se valora la capacidad de inhibición de la respuesta cutánea a la histamina por parte de la terfenadina en relación al placebo en cuarenta pacientes atópicos asintomáticos del servicio de Alergología e Inmunología del HG-1, encontrándose que la terfenadina se muestra más efectiva para inhibir el desarrollo del habón urticario ocasionado por la administración intradérmica de una solución de histamina que el placebo, con una potencia bloqueadora de los receptores histamínicos periféricos H1 semejante a la clemastina y al ketotifeno, y sin efectos colaterales atribuibles a ella en los veinte pacientes que la recibieron

effect of histamine receptor blockers [mepyramine maleate and cimetidine], on experimental acute portal hypertension

This work aimed to study the effect of H1 and H2-receptors blockers on the portal venous pressure separately and in combination. Experimental portal hypertension was done by clamping the portal vein of dogs, simulating what happens in schistosomal hepatic fibrosis. H1-receptor blocker [mepyramine maleate] was used in five dogs, H2-receptor blocker [cimetidine] was used in five dogs, and in other five dogs both H1 and H2-receptor blockers were used. It was found that the synergestic action of both H1 and H2-receptor blockers causes more lowering of the portal blood pressure than using any of them alone, which is helpful in bleeding esophageal varices

Central histaminoceptor-adrenoceptor interrelations in the release of adrenocorticotrophic hormone.

Intracerebroventricular administration of adrenaline, noradrenaline phenylephrine, clonidine and histamine produced a significant rise in plasma cortisol concentration whereas isoprenaline had no effect. alpha-Adrenoceptor blockers (yohimbine or piperoxon) per se did not alter the plasma cortisol level. Central pretreatment with yohimbine or piperoxin, blocked the rise in plasma cortisol level induced by icv noradrenaline, phenylephrine and clonidine. In another set of experiments, both H1 and H2 receptor antagonists (mepyramine, and metiamide) per se had not significant effect on plasma cortisol concentration. Central histamine induced rise in plasma cortisol concentration was significantly blocked by icv pretreatment with both H1 and H2 receptor blockers. Furthermore, yohimbine also significantly prevented the rise of plasma cortisol level induced by icv histamine.

Effects of changes in pH of bath fluid on isolated guinea pig ileum preparation.

The effects of changes in the pH of Tyrode's solution on the responses of isolated guinea pig ileum preparation to acetylcholine and histamine were studied. At higher levels of pH (increased alkalinity), the responses of the tissue to both acetylcholine and histamine were increased. At lower pH levels (increased acidity), the response of the tissue to acetylcholine was increased but that to histamine was reduced.