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Neurosci."],"published-print":{"date-parts":[[2004,10,27]]},"abstract":"<jats:p>Using whole-cell patch-clamp methods, we examined the hypothesis that serotonin [5-hydroxytryptamine (5-HT)] receptor activation enhances TRPV1 function in mouse colon sensory neurons in lumbosacral dorsal root ganglia, which were identified by retrograde labeling with DiI (1,1\u2032-dioctadecyl-3,3,3\u2032,3-tetramethlindocarbocyanine methanesulfonate) injected into multiple sites in the wall of the descending colon. 5-HT increased membrane excitability at a temperature below body temperature in response to thermal ramp stimuli in colon sensory neurons from wild-type mice, but not from TRPV1 knock-out mice. 5-HT significantly enhanced capsaicin-, heat-, and proton-evoked currents with an EC<jats:sub>50<\/jats:sub>value of 2.2 \u03bc<jats:sc>m<\/jats:sc>. 5-HT (1 \u03bc<jats:sc>m<\/jats:sc>) significantly increased capsaicin-evoked (100 n<jats:sc>m<\/jats:sc>) and proton-evoked (pH 5.5) currents 1.6- and 4.7-fold, respectively, and significantly decreased the threshold temperature for heat current activation from 42 to 38\u00b0C. The enhancement of TRPV1 by 5-HT was significantly attenuated by selective 5-HT<jats:sub>2<\/jats:sub>and 5-HT<jats:sub>4<\/jats:sub>receptor antagonists, but not by a 5-HT<jats:sub>3<\/jats:sub>receptor antagonist. In support, 5-HT<jats:sub>2<\/jats:sub>and 5-HT<jats:sub>4<\/jats:sub>receptor agonists mimicked the facilitating effects of 5-HT on TRPV1 function. Downstream signaling required G-protein activation and phosphorylation as intracellularly administered GDP-\u03b2-S [guanosine 5\u2032-<jats:italic>O<\/jats:italic>-(2-thiodiphosphate], protein kinase A inhibitors, and an A-kinase anchoring protein inhibitor significantly blocked serotonergic facilitation of TRPV1 function; 5-HT<jats:sub>2<\/jats:sub>receptor-mediated facilitation was also inhibited by a PKC inhibitor. We conclude that the facilitation of TRPV1 by metabotropic 5-HT receptor activation may contribute to hypersensitivity of primary afferent neurons in irritable bowel syndrome patients.<\/jats:p>","DOI":"10.1523\/jneurosci.2639-04.2004","type":"journal-article","created":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T01:01:35Z","timestamp":1098925295000},"page":"9521-9530","source":"Crossref","is-referenced-by-count":124,"title":["TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation"],"prefix":"10.1523","volume":"24","author":[{"given":"Takeshi","family":"Sugiuar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Bielefeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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