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5‐HT 2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria
Author(s) -
Moro Christian,
Edwards Lily,
ChessWilliams Russ
Publication year - 2016
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13172
Subject(s) - lamina propria , urothelium , medicine , endocrinology , serotonin , 5 ht receptor , arginine , receptor antagonist , carbachol , antagonist , receptor , chemistry , urinary bladder , epithelium , biochemistry , amino acid , pathology
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‐HT 1&2 , 100 nmol/L), RS102221 (5‐HT 2C , 30 nmol/L), ondansetron (5‐HT 3 , 30 nmol/L), GR113808, (5‐HT 4 , 100 nmol/L), SB699551 (5‐HT 5 , 10 nmol/L), SB399885 (5‐HT 6 , 100 nmol/L) and SB269970 (5‐HT 7 , 10 nmol/L) did not influence responses to 5‐HT. However, the 5‐HT 2A 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‐HT 2A receptor.