5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria

ObjectivesTo examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments. MethodsStrips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, N-nitro-l-arginine and indomethacin. Responses to -methyl-5-HT were also examined. ResultsStrips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of N-nitro-l-arginine (100 mol/L) or indomethacin (5 mol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2, 100 nmol/L), RS102221 (5-HT2C, 30 nmol/L), ondansetron (5-HT3, 30 nmol/L), GR113808, (5-HT4, 100 nmol/L), SB699551 (5-HT5, 10 nmol/L), SB399885 (5-HT6, 100 nmol/L) and SB269970 (5-HT7, 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 mol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9. ConclusionsThe results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.