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

OBJECTIVES: To 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.

METHODS: Strips 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, Nω-nitro-l-arginine and indomethacin. Responses to α-methyl-5-HT were also examined.

RESULTS: Strips 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 Nω-nitro-l-arginine (100 μmol/L) or indomethacin (5 μmol/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 μmol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9.

CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.