The functional role of 5-HT receptors on visceral sensation of pelvic organs

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The epitheliums of urinary bladder, esophagus, and colorectum release ATP in response to various stimuli, which contributes to the transmission of visceral sensation including visceral pain. We investigated the involvement of 5-HT receptors and their downstream signals on the ATP release from these epitheliums. In the epithelium of urinary bladder (urothelium), 5-HT1D and 5-HT4 were expressed. Serotonin suppressed the distention-induced ATP release from urothelium via 5-HT1D. The ATP release was facilitated by cAMP, which was reduced by 5-HT1D. In the esophageal epithelium, none of the 5-HT receptor subtypes was expressed and functioned. In the colorectal epithelium, only 5-HT4 was expressed and inhibited the ATP release. These data suggested that the urothelium-specific 5-HT1D is a candidate for the therapeutic target for the visceral hypersensitivity of urinary bladder.