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1.
BMC Physiol ; 13: 5, 2013 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-23394313

RESUMEN

BACKGROUND: Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5. RESULTS: Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g) and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g) after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice. CONCLUSION: Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.


Asunto(s)
Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Quinina/farmacología , Aumento de Peso/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Composición Corporal/efectos de los fármacos , Dieta Alta en Grasa , Suplementos Dietéticos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Canales Catiónicos TRPM/metabolismo , Triglicéridos/metabolismo
2.
Int J Sport Nutr Exerc Metab ; 23(6): 584-92, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23689036

RESUMEN

Recent studies have demonstrated a direct link between increased exogenous CHO oxidation (CHOexog) and enhanced performance. The limiting factor for CHOexog appears to be at the level of intestinal transporters, with sodium/glucose cotransporter 1 (SGLT1) and glucose transporter Type 5 (GLUT5) responsible for glucose and fructose transport, respectively. Studies in animal models have shown that SGLT1 and intestinal glucose uptake are up-regulated by high carbohydrate diets or noncaloric sweeteners. The aim of this study was to determine the effect of preexercise ingestion of noncaloric sweeteners on CHOexog during exercise in athletes. In a randomized, crossover, double-blind fashion twenty-three healthy male cyclists (age = 29 ± 7 yrs, mass = 73.6 ± 7.4 kg, VO2peak = 68.3 ± 9.3 ml/kg/min) consumed 8 × 50 ml doses of either placebo (CON) or 1mM sucralose (SUCRA) every 15 min starting 120 min before the onset of exercise. This was followed by 2h of cycling at 48.5 ± 8.6% of VO2peak with continual ingestion of a maltodextrin drink (1.2 g/min; 828 ml/ hr). Average CHOexog during the first hour of exercise did not differ between SUCRA and CON conditions (0.226 ± 0.081 g/min vs. 0.212 ± 0.076 g/min, Δ =0.015 g/min, 95% CI -0.008 g/min, 0.038 g/min, p = .178). Blood glucose, plasma insulin and lactate, CHO and fat substrate utilization, heart rate, ratings of perceived exertion, and gastrointestinal symptoms did not differ between conditions. Our data suggest that consumption of noncaloric sweeteners in the immediate period before exercise does not lead to a significant increase in CHOexog during exercise.


Asunto(s)
Ciclismo/fisiología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Ejercicio Físico/fisiología , Fenómenos Fisiológicos en la Nutrición Deportiva , Sacarosa/análogos & derivados , Adulto , Glucemia/metabolismo , Estudios Cruzados , Método Doble Ciego , Metabolismo Energético , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Transportador de Glucosa de Tipo 5/genética , Transportador de Glucosa de Tipo 5/metabolismo , Frecuencia Cardíaca , Humanos , Insulina/sangre , Ácido Láctico/sangre , Masculino , Oxidación-Reducción/efectos de los fármacos , Consumo de Oxígeno , Resistencia Física , Polisacáridos/administración & dosificación , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo , Sacarosa/administración & dosificación , Adulto Joven
3.
J Neurosci ; 30(25): 8376-82, 2010 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-20573884

RESUMEN

The oral perception of fat has traditionally been considered to rely mainly on texture and olfaction, but recent findings suggest that taste may also play a role in the detection of long chain fatty acids. The two G-protein coupled receptors GPR40 (Ffar1) and GPR120 are activated by medium and long chain fatty acids. Here we show that GPR120 and GPR40 are expressed in the taste buds, mainly in type II and type I cells, respectively. Compared with wild-type mice, male and female GPR120 knock-out and GPR40 knock-out mice show a diminished preference for linoleic acid and oleic acid, and diminished taste nerve responses to several fatty acids. These results show that GPR40 and GPR120 mediate the taste of fatty acids.


Asunto(s)
Ácidos Grasos , Preferencias Alimentarias/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Papilas Gustativas/metabolismo , Gusto/fisiología , Animales , Femenino , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Receptores Acoplados a Proteínas G/genética
4.
Nutrients ; 13(11)2021 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-34836151

RESUMEN

Fermentation is an ancient food preservation process, and fermented products have been traditionally consumed in different cultures worldwide over the years. The interplay between human gut microbiota, diet and host health is widely recognized. Diet is one of the main factors modulating gut microbiota potentially with beneficial effects on human health. Fermented dairy products have received much attention, but other sources of probiotic delivery through food received far less attention. In this research, a combination of in vitro tools mimicking colonic fermentation and the intestinal epithelium have been applied to study the effect of different pasteurized and non-pasteurized water kefir products on gut microbiota, epithelial barrier function and immunomodulation. Water kefir increased beneficial short-chain fatty acid production at the microbial level, reduced detrimental proteolytic fermentation compounds and increased Bifidobacterium genus abundance. The observed benefits are enhanced by pasteurization. Pasteurized products also had a significant effect at the host level, improving inflammation-induced intestinal epithelial barrier disruption and increasing IL-10 and IL-1ß compared to the control condition. Our data support the potential health benefits of water kefir and demonstrate that pasteurization, performed to prolong shelf life and stability of the product, also enhanced these benefits.


Asunto(s)
Bebidas/análisis , Citocinas/biosíntesis , Microbioma Gastrointestinal , Kéfir , Agua/farmacología , Colon/metabolismo , Colon/microbiología , Ácidos Grasos Volátiles/biosíntesis , Fermentación , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Pasteurización , Permeabilidad
5.
J Neurosci ; 29(8): 2654-62, 2009 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-19244541

RESUMEN

Complex tasting divalent salts (CTDS) are present in our daily diet, contributing to multiple poorly understood taste sensations. CTDS evoking metallic, bitter, salty, and astringent sensations include the divalent salts of iron, zinc, copper, and magnesium. To identify pathways involved with the complex perception of the above salts, taste preference tests (two bottles, brief access) were performed in wild-type (WT) mice and in mice lacking (1) the T1R3 receptor, (2) TRPV1, the capsaicin receptor, or (3) the TRPM5 channel, the latter being necessary for the perception of sweet, bitter, and umami tasting stimuli. At low concentrations, FeSO(4) and ZnSO(4) were perceived as pleasant stimuli by WT mice, and this effect was fully reversed in TRPM5 knock-out mice. In contrast, MgSO(4) and CuSO(4) were aversive to WT mice, but for MgSO(4) the aversion was abolished in TRPM5 knock-out animals, and for CuSO(4), aversion decreased in both TRPV1- and TRPM5-deficient animals. Behavioral tests revealed that the T1R3 subunit of the sweet and umami receptors is implicated in the hedonically positive perception of FeSO(4) and ZnSO(4). For high concentrations of CTDS, the omission of TRPV1 reduced aversion. Imaging studies on heterologously expressed TRPM5 and TRPV1 channels are consistent with the behavioral experiments. Together, these results rationalize the complexity of metallic taste by showing that at low concentrations, compounds such as FeSO(4) and ZnSO(4) stimulate the gustatory system through the hedonically positive T1R3-TRPM5 pathway, and at higher concentrations, their aversion is mediated, in part, by the activation of TRPV1.


Asunto(s)
Preferencias Alimentarias/fisiología , Sales (Química) , Canales Catiónicos TRPM/fisiología , Canales Catiónicos TRPV/fisiología , Gusto/fisiología , Animales , Capsaicina/farmacología , Línea Celular Transformada , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Sulfato de Cobre/farmacología , Relación Dosis-Respuesta a Droga , Conducta de Ingestión de Líquido/efectos de los fármacos , Femenino , Compuestos Ferrosos/farmacología , Preferencias Alimentarias/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Humanos , Modelos Lineales , Sulfato de Magnesio/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutagénesis Sitio-Dirigida/métodos , Unión Proteica/efectos de los fármacos , Sales (Química)/farmacología , Canales Catiónicos TRPM/deficiencia , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPV/deficiencia , Canales Catiónicos TRPV/genética , Gusto/efectos de los fármacos , Gusto/genética , Transfección , Sulfato de Zinc/farmacología
7.
Front Microbiol ; 11: 572921, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33042082

RESUMEN

The gut microbiota is a new frontier in health and disease. Not only many diseases are associated with perturbed microbiota, but an increasing number of studies point to a cause-effect relationship. Defining a healthy microbiota is not possible at the current state of our knowledge mostly because of high interindividual variability. A resilient microbiota could be used as surrogate for healthy microbiota. In addition, the gut microbiota is an "organ" with frontline exposure to environmental changes and insults. During the lifetime of an individual, it is exposed to challenges such as unhealthy diet, medications and infections. Impaired ability to bounce back to the pre-challenge baseline may lead to dysbiosis. It is therefore legitimate to postulate that maintaining a resilient microbiota may be important for health. Here we review the concept of resilience, what is known about the characteristics of a resilient microbiota, and how to assess microbiota resilience experimentally using a model of high fat diet challenge in humans. Interventions to maintain microbiota resilience can be guided by the knowledge of what microbial species or functions are perturbed by challenges, and designed to replace diminished species with probiotics, when available, or boost them with prebiotics. Fibers with multiple structures and composition can also be used to increase microbiota diversity, a characteristic of the microbiota that may be associated with resilience. We finally discuss some open questions and knowledge gaps.

8.
Sci Rep ; 10(1): 16117, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32999316

RESUMEN

Numerous benefits of breastfeeding over infant formula are fully established. The superiority of human milk over bovine milk-based formula is partly due to human milk oligosaccharides (HMOs), a family of over 100 molecules present specifically and substantially in human milk that resemble mucosal glycans. To uncover novel physiological functions and pathways of HMOs, we screened a panel of 165 G-protein coupled receptors (GPCRs) using a blend of 6 HMOs (3'-O-sialyllactose (3'SL), 6'-O-sialyllactose (6'SL), lacto-N-tetraose (LNT), lacto-N-neo-tetraose (LNnT), 2-O-fucosyllactose (2'FL), and difucosyllactose (diFL)), and followed up positive hits with standard receptor assays. The HMO blend specifically activated GPR35. LNT and 6'SL individually activated GPR35, and they showed synergy when used together. In addition, in vitro fermentation of infant stool samples showed that 2'FL upregulates the production of the GPR35 agonist kynurenic acid (KYNA) by the microbiota. LNT + 6'SL and KYNA showed additive activation of GPR35. Activation by 6'SL and LNT of GPR35, a receptor mediating attenuation of pain and colitis, is to our knowledge the first demonstration of GPCR activation by any HMO. In addition, we demonstrated a remarkable cooperation between nutrition and microbiota towards activation of a host receptor highlighting the close interplay between environment and host-microbe interactions.


Asunto(s)
Leche Humana/metabolismo , Oligosacáridos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/fisiología , Animales , Lactancia Materna/métodos , Bovinos , Proteínas de Unión al GTP/metabolismo , Interacciones Microbiota-Huesped/fisiología , Humanos , Lactante , Fórmulas Infantiles , Lactosa/análogos & derivados , Lactosa/metabolismo , Trisacáridos/metabolismo
9.
Biochem Biophys Res Commun ; 376(4): 653-7, 2008 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-18804451

RESUMEN

Artificial sweeteners such as saccharin, aspartame, acesulfame-K, and cyclamate produce at high concentrations an unpleasant after-taste that is generally attributed to bitter and metallic taste sensations. To identify receptors involved with the complex perception of the above compounds, preference tests were performed in wild-type mice and mice lacking the TRPV1 channel or the T1R3 receptor, the latter being necessary for the perception of sweet taste. The sweeteners, including cyclamate, displayed a biphasic response profile, with the T1R3 mediated component implicated in preference. At high concentrations imparting off-taste, omission of TRPV1 reduced aversion. In a heterologous expression system the Y511A point mutation in the vanilloid pocket of TRPV1 did not affect saccharin and aspartame responses but abolished cyclamate and acesulfame-K activities. The results rationalize artificial sweetener tastes and off-tastes by showing that at low concentrations, these molecules stimulate the gustatory system through the hedonically positive T1R3 pathway, and at higher concentrations, their aversion is partly mediated by TRPV1.


Asunto(s)
Receptores Acoplados a Proteínas G/fisiología , Edulcorantes/metabolismo , Canales Catiónicos TRPV/fisiología , Gusto/fisiología , Animales , Humanos , Ratones , Ratones Noqueados , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Edulcorantes/farmacología , Canales Catiónicos TRPV/agonistas , Canales Catiónicos TRPV/genética , Gusto/efectos de los fármacos , Gusto/genética
10.
BMC Neurosci ; 9: 96, 2008 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-18831764

RESUMEN

BACKGROUND: Anatomical tracing of neural circuits originating from specific subsets of taste receptor cells may shed light on interactions between taste cells within the taste bud and taste cell-to nerve interactions. It is unclear for example, if activation of type II cells leads to direct activation of the gustatory nerves, or whether the information is relayed through type III cells. To determine how WGA produced in T1r3-expressing taste cells is transported into gustatory neurons, transgenic mice expressing WGA-IRES-GFP driven by the T1r3 promoter were generated. RESULTS: Immunohistochemistry showed co-expression of WGA, GFP and endogenous T1r3 in the taste bud cells of transgenic mice: the only taste cells immunoreactive for WGA were the T1r3-expressing cells. The WGA antibody also stained intragemmal nerves. WGA, but not GFP immunoreactivity was found in the geniculate and petrosal ganglia of transgenic mice, indicating that WGA was transported across synapses. WGA immunoreactivity was also found in the trigeminal ganglion, suggesting that T1r3-expressing cells make synapses with trigeminal neurons. In the medulla, WGA was detected in the nucleus of the solitary tract but also in the nucleus ambiguus, the vestibular nucleus, the trigeminal nucleus and in the gigantocellular reticular nucleus. WGA was not detected in the parabrachial nucleus, or the gustatory cortex. CONCLUSION: These results show the usefulness of genetically encoded WGA as a tracer for the first and second order neurons that innervate a subset of taste cells, but not for higher order neurons, and demonstrate that the main route of output from type II taste cells is the gustatory neuron, not the type III cells.


Asunto(s)
Receptores Acoplados a Proteínas G/metabolismo , Sinapsis/metabolismo , Papilas Gustativas/metabolismo , Aglutininas del Germen de Trigo/metabolismo , Animales , Ganglio Geniculado/citología , Ganglio Geniculado/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Inmunohistoquímica , Bulbo Raquídeo/citología , Bulbo Raquídeo/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Confocal , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiología , Regiones Promotoras Genéticas/genética , Transporte de Proteínas , Receptores Acoplados a Proteínas G/genética , Núcleo Solitario/citología , Núcleo Solitario/metabolismo , Sinapsis/fisiología , Papilas Gustativas/citología , Ganglio del Trigémino/citología , Ganglio del Trigémino/metabolismo , Aglutininas del Germen de Trigo/genética
11.
EMBO Mol Med ; 10(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29343498

RESUMEN

Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely induced O2 consumption, through GPR120-dependent and GPR120-independent mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP1. Collectively, these data suggest that activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising strategy to increase lipid combustion and reduce obesity.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Compuestos de Bifenilo/farmacología , Mitocondrias/metabolismo , Fenilpropionatos/farmacología , Receptores Acoplados a Proteínas G/agonistas , Adipocitos Marrones/citología , Adipocitos Marrones/efectos de los fármacos , Adipocitos Marrones/metabolismo , Adipocitos Blancos/citología , Adipocitos Blancos/efectos de los fármacos , Adipocitos Blancos/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Adiposidad/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Respiración de la Célula/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Lípidos , Masculino , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Modelos Biológicos , Oxidación-Reducción , Consumo de Oxígeno/efectos de los fármacos , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/metabolismo , Proteína Desacopladora 1/metabolismo
12.
J Comp Neurol ; 502(6): 1003-11, 2007 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-17447253

RESUMEN

Tight junctions operate as semipermeable barriers in epithelial tissue, separating the apical from the basolateral sides of the cells. Membrane proteins of the claudin family represent the major tight junction constituents, and some reinforce permeability barriers, whereas others create pores based on solute size and ion selectivity. To outline paracellular permeability pathways in gustatory tissue, all claudins expressed in mouse taste buds and in human fungiform papillae have been characterized. Twelve claudins are expressed in murine taste-papillae-enriched tissue, and five of those are expressed in human fungiform papillae. A subset of the claudins expressed in mouse papillae is uniquely found in taste buds. By immunohistochemistry, claudin 4 has been found in mouse taste epithelium, with high abundance around the taste pore. Claudin 6 is explicitly detected inside the pore, claudin 7 was found at the basolateral side of taste cells, and claudin 8 was found around the pore. With the ion permeability features of the different claudins, a highly specific permeability pattern for paracellular diffusion is apparent, which indicates a peripheral mechanism for taste coding.


Asunto(s)
Permeabilidad de la Membrana Celular/fisiología , Membrana Celular/metabolismo , Proteínas de la Membrana/metabolismo , Papilas Gustativas/metabolismo , Gusto/fisiología , Uniones Estrechas/metabolismo , Animales , Comunicación Celular/fisiología , Membrana Celular/ultraestructura , Claudina-4 , Claudinas , Difusión , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Papilas Gustativas/ultraestructura , Uniones Estrechas/ultraestructura
13.
BMC Biol ; 4: 7, 2006 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-16573824

RESUMEN

BACKGROUND: Taste receptor cells are responsible for transducing chemical stimuli from the environment and relaying information to the nervous system. Bitter, sweet and umami stimuli utilize G-protein coupled receptors which activate the phospholipase C (PLC) signaling pathway in Type II taste cells. However, it is not known how these cells communicate with the nervous system. Previous studies have shown that the subset of taste cells that expresses the T2R bitter receptors lack voltage-gated Ca2+ channels, which are normally required for synaptic transmission at conventional synapses. Here we use two lines of transgenic mice expressing green fluorescent protein (GFP) from two taste-specific promoters to examine Ca2+ signaling in subsets of Type II cells: T1R3-GFP mice were used to identify sweet- and umami-sensitive taste cells, while TRPM5-GFP mice were used to identify all cells that utilize the PLC signaling pathway for transduction. Voltage-gated Ca2+ currents were assessed with Ca2+ imaging and whole cell recording, while immunocytochemistry was used to detect expression of SNAP-25, a presynaptic SNARE protein that is associated with conventional synapses in taste cells. RESULTS: Depolarization with high K+ resulted in an increase in intracellular Ca2+ in a small subset of non-GFP labeled cells of both transgenic mouse lines. In contrast, no depolarization-evoked Ca2+ responses were observed in GFP-expressing taste cells of either genotype, but GFP-labeled cells responded to the PLC activator m-3M3FBS, suggesting that these cells were viable. Whole cell recording indicated that the GFP-labeled cells of both genotypes had small voltage-dependent Na+ and K+ currents, but no evidence of Ca2+ currents. A subset of non-GFP labeled taste cells exhibited large voltage-dependent Na+ and K+ currents and a high threshold voltage-gated Ca2+ current. Immunocytochemistry indicated that SNAP-25 was expressed in a separate population of taste cells from those expressing T1R3 or TRPM5. These data indicate that G protein-coupled taste receptors and conventional synaptic signaling mechanisms are expressed in separate populations of taste cells. CONCLUSION: The taste receptor cells responsible for the transduction of bitter, sweet, and umami stimuli are unlikely to communicate with nerve fibers by using conventional chemical synapses.


Asunto(s)
Canales de Calcio/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteína 25 Asociada a Sinaptosomas/metabolismo , Canales Catiónicos TRPM/metabolismo , Papilas Gustativas/citología , Papilas Gustativas/metabolismo , Animales , Calcio/metabolismo , Regulación de la Expresión Génica , Genotipo , Ratones , Ratones Transgénicos , Potasio/metabolismo , Regiones Promotoras Genéticas , Receptores de Superficie Celular/genética , Transducción de Señal , Canales Catiónicos TRPM/genética , Papilas Gustativas/ultraestructura , Fosfolipasas de Tipo C
14.
J Neurosci ; 24(35): 7674-80, 2004 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-15342734

RESUMEN

The sense of taste comprises at least five distinct qualities: sweet, bitter, sour, salty, and umami, the taste of glutamate. For bitter, sweet, and umami compounds, taste signaling is initiated by binding of tastants to G-protein-coupled receptors in specialized epithelial cells located in the taste buds, leading to the activation of signal transduction cascades. Alpha-gustducin, a taste cell-expressed G-protein alpha subunit closely related to the alpha-transducins, is a key mediator of sweet and bitter tastes. Alpha-gustducin knock-out (KO) mice have greatly diminished, but not entirely abolished, responses to many bitter and sweet compounds. We set out to determine whether alpha-gustducin also mediates umami taste and whether rod alpha-transducin (alpha(t-rod)), which is also expressed in taste receptor cells, plays a role in any of the taste responses that remain in alpha-gustducin KO mice. Behavioral tests and taste nerve recordings of single and double KO mice lacking alpha-gustducin and/or alpha(t-rod) confirmed the involvement of alpha-gustducin in bitter (quinine and denatonium) and sweet (sucrose and SC45647) taste and demonstrated the involvement of alpha-gustducin in umami [monosodium glutamate (MSG), monopotassium glutamate (MPG), and inosine monophosphate (IMP)] taste as well. We found that alpha(t-rod) played no role in taste responses to the salty, bitter, and sweet compounds tested or to IMP but was involved in the umami taste of MSG and MPG. Umami detection involving alpha-gustducin and alpha(t-rod) occurs in anteriorly placed taste buds, however taste cells at the back of the tongue respond to umami compounds independently of these two G-protein subunits.


Asunto(s)
Glutamatos , Inosina Monofosfato , Glutamato de Sodio , Papilas Gustativas/fisiología , Gusto/fisiología , Transducina/fisiología , Animales , Nervio de la Cuerda del Tímpano/fisiología , Cruzamientos Genéticos , Preferencias Alimentarias , Genotipo , Nervio Glosofaríngeo/fisiología , Guanidinas , Glicoproteínas de Membrana/fisiología , Ratones , Ratones Noqueados , Compuestos de Amonio Cuaternario , Quinina , Receptores de Superficie Celular/fisiología , Sacarosa , Receptores Toll-Like , Transducina/deficiencia , Transducina/genética
16.
Chem Senses ; 32(1): 41-9, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17030556

RESUMEN

The taste system, made up of taste receptor cells clustered in taste buds at the surface of the tongue and the soft palate, plays a key role in the decision to ingest or reject food and thereby is essential in protecting organisms against harmful toxins and in selecting the most appropriate nutrients. To determine if a similar chemosensory system exists in the gastrointestinal tract, we used immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate which taste-signaling molecules are expressed in the intestinal mucosa. The PCR data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2 (PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of mice and humans, with the exception of T1r2, which was not detected in the mouse and human stomach or in the mouse colon. Using transgenic mice expressing enhanced green fluorescent protein under the control of the Trpm5 promoter, we found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3 in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2. The data suggest that these duodenal cells are possibly involved in sensing amino acids.


Asunto(s)
Mucosa Intestinal/metabolismo , Proteínas/metabolismo , Transducción de Señal , Gusto , Animales , Secuencia de Bases , Cartilla de ADN , Ingestión de Energía , Humanos , Inmunohistoquímica , Mucosa Intestinal/citología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
17.
Chem Senses ; 31(6): 573-80, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16740645

RESUMEN

The importance of alpha-gustducin in sweet taste transduction is based on data obtained with sucrose and the artificial sweetener SC45647. Here we studied the role of alpha-gustducin in sweet taste. We compared the behavioral and electrophysiological responses of alpha-gustducin knockout (KO) and wild-type (WT) mice to 11 different sweeteners, representing carbohydrates, artificial sweeteners, and sweet amino acids. In behavioral experiments, over 48-h preference ratios were measured in two-bottle preference tests. In electrophysiological experiments, integrated responses of chorda tympani (CT) and glossopharyngeal (NG) nerves were recorded. We found that preference ratios of the KO mice were significantly lower than those of WT for acesulfame-K, dulcin, fructose, NC00174, D-phenylalanine, L-proline, D-tryptophan, saccharin, SC45647, sucrose, but not neotame. The nerve responses to all sweeteners, except neotame, were smaller in the KO mice than in the WT mice. The differences between the responses in WT and KO mice were more pronounced in the CT than in the NG. These data indicate that alpha-gustducin participates in the transduction of the sweet taste in general.


Asunto(s)
Carbohidratos/farmacología , Compuestos de Fenilurea/farmacología , Gusto/efectos de los fármacos , Gusto/fisiología , Transducina/deficiencia , Transducina/metabolismo , Animales , Conducta Animal , Masculino , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Soluciones , Transducina/genética
18.
Chem Senses ; 31(3): 253-64, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16436689

RESUMEN

Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A previous study reported that mice with an internal deletion of Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste-mediated responses to bitter, sweet, and umami compounds. We independently generated knockout mice null for Trpm5 protein expression due to deletion of Trpm5's promoter region and exons 1-4 (including the translation start site). We examined the taste-mediated responses of Trpm5 null mice and wild-type (WT) mice using three procedures: gustatory nerve recording [chorda tympani (CT) and glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but not abolished, avoidance (as indicated by licking responses and preference ratios higher than those of WT), a normal CT response, and a greatly diminished NG response. With sweet compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, and absent or greatly reduced nerve responses. With umami compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, a normal NG response, and a greatly diminished CT response. Our results demonstrate that the consequences of eliminating Trmp5 expression vary depending upon the taste quality and the lingual taste field examined. Thus, while Trpm5 is an important factor in many taste responses, its absence does not eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5-independent pathways underlie bitter, sweet, and umami tastes.


Asunto(s)
Quinina/farmacología , Glutamato de Sodio/farmacología , Edulcorantes/farmacología , Canales Catiónicos TRPM/fisiología , Gusto/fisiología , Animales , Conducta Animal/efectos de los fármacos , Nervio de la Cuerda del Tímpano/fisiología , Relación Dosis-Respuesta a Droga , Eliminación de Gen , Nervio Glosofaríngeo/fisiología , Ácido Clorhídrico/farmacología , Ratones , Ratones Noqueados , Compuestos de Amonio Cuaternario/farmacología , Tiempo de Reacción/fisiología , Cloruro de Sodio/farmacología , Estimulación Química , Canales Catiónicos TRPM/genética , Gusto/genética
19.
Chem Senses ; 30(4): 299-316, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15800219

RESUMEN

We examined the necessity of alpha-gustducin, a G protein alpha-subunit expressed in taste cells, to taste-mediated licking responses of mice to sapid stimuli. To this end, we measured licking responses of alpha-gustducin knock-out (Gus-/-) mice and heterozygotic littermate controls (Gus+/-) to a variety of 'bitter', 'umami', 'sweet', 'salty' and 'sour' taste stimuli. All previous studies of how Gus-/- mice ingest taste stimuli have used long-term (i.e. 48 h) preference tests, which may be confounded by post-ingestive and/or experiential effects of the taste stimuli. We minimized these confounds by using a brief-access taste test, which quantifies immediate lick responses to extremely small volumes of sapid solutions. We found that deleting alpha-gustducin (i) dramatically reduced the aversiveness of a diverse range of 'bitter' taste stimuli; (ii) moderately decreased appetitive licking to low and intermediate concentrations of an 'umami' taste stimulus (monosodium glutamate in the presence of 100 microM amiloride), but virtually eliminated the normal aversion to high concentrations of the same taste stimulus; (iii) slightly decreased appetitive licking to 'sweet' taste stimuli; and (iv) modestly reduced the aversiveness of high, but not low or intermediate, concentrations of NaCl. There was no significant effect of deleting alpha-gustducin on licking responses to NH4Cl or HCl.


Asunto(s)
Conducta Alimentaria/fisiología , Papilas Gustativas/fisiología , Gusto/fisiología , Transducina/fisiología , Animales , Privación de Alimentos/fisiología , Preferencias Alimentarias/fisiología , Masculino , Ratones , Ratones Noqueados , Transducina/genética , Privación de Agua/fisiología
20.
Chem Senses ; 27(8): 719-27, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12379596

RESUMEN

The transduction of responses to bitter and sweet compounds utilizes guanine nucleotide binding proteins (G proteins) and their coupled receptors. Alpha-gustducin, a transducin-like G protein alpha-subunit, and rod alpha-transducin are expressed in taste receptor cells. Alpha-gustducin knockout mice have profoundly diminished behavioral and electrophysiological responses to many bitter and sweet compounds, although these mice retain residual responses to these compounds. Alpha-gustducin and rod alpha-transducin are biochemically indistinguishable in their in vitro interactions with retinal phosphodiesterase, rhodopsin and G protein betagamma-subunits. To determine if alpha-transducin can function in taste receptor cells and to compare the function of alpha-gustducin versus alpha-transducin in taste transduction in vivo, we generated transgenic mice that express alpha-transducin under the control of the alpha-gustducin promoter in the alpha-gustducin null background. Immunohistochemistry showed that the alpha-transducin transgene was expressed in about two-thirds of the alpha-gustducin lineage of taste receptor cells. Two-bottle preference tests showed that transgenic expression of rod alpha-transducin partly rescued responses to denatonium benzoate, sucrose and the artificial sweetener SC45647, but not to quinine sulfate. Gustatory nerve recordings showed a partial rescue by the transgene of the response to sucrose, SC45647 and quinine, but not to denatonium. These results demonstrate that alpha-transducin can function in taste receptor cells and transduce some taste cell responses. Our results also suggest that alpha-transducin and alpha-gustducin may differ, at least in part, in their function in these cells, although this conclusion must be qualified because of the limited fidelity of the transgene expression.


Asunto(s)
Gusto/fisiología , Transducina/fisiología , Analgésicos no Narcóticos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Proteínas Fluorescentes Verdes , Guanidinas/farmacología , Inmunohistoquímica , Proteínas Luminiscentes/metabolismo , Ratones , Ratones Noqueados , Ratones Transgénicos , Microscopía Fluorescente , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Compuestos de Amonio Cuaternario/farmacología , Quinina/farmacología , Sacarosa/farmacología , Edulcorantes/farmacología , Gusto/genética , Papilas Gustativas/fisiología , Transducina/genética , Transgenes
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