5-Hydroxytryptamine potentiates neurogenic contractions of rat isolated urinary bladder through both 5-HT7 and 5-HT2C receptors

Serotonin (5-HT) enhances the neurogenic contractile response induced by electrical field stimulation (IFS) in the rat isolated urinary bladder The aim of this study was to functionally characterize the receptors involved in this effect by using a range of 5-HT receptor subtype selective agonists and antagonists 5 HT produced a concentration-dependent potentiation of contractile responses to EFS with a pEC(50) value of 686 +/- 024 SB-269970 (0 01 +/- 0 1 and 1 mu M) a selective 5 FM reo ptor antagonist caused a concentration dependent rightward shift of the 5-HT induced response The pA(2) value was 8 16 with a slope of 046 +/- 0 08 Neither ketanserine nor SB 204741 5-HT2A and 5-HT2B receptors antagonists respectively affected the concentration-response curve to 5 HT However 5-HT response was antagonized by the selective 5-HT2C receptor antagonist SB-242084 (0 1 and 1 mu M) In the presence of 1 mu M of both antagonists SB 269970 and SB-242084 5-HT response was almost fully inhibited 5-CT a 5 HT7 receptor agonist Induced a biphasic concentration-dependent potentiation of neurogenic contractions SB 269970 concentration-dependently antagonized the first phase of 5-CT response with a pA(2) value of 877 and a slope not significantly different from unity (0 91 +/- 0 11) that suggests a competitive antagonism WAY-161503 a 5 HT2C receptor agonist (001-10 mu M) induced a concentration-dependent potentiation of contractile response to EFS while DOI (a selective 5-HT2A agonist) had no effect SB-242084 (0 1 and 1 mu M) antagonized the effect of WAY-161503 in a concentration-dependent manner The current results demonstrate that 5-HT potentiates neurogenic contractions of rat Isolated detrusor muscle through both 5-HT7 and 5-HT2C receptors (C) 2010 Elsevier B V All rights resented