Pharmacological analysis of 5-hydroxytryptamine effects on human isolated ureter

Abstract

5-Hydroxytryptamine (5-HT) induced concentration-dependent contractions in human isolated ureteral strips in vivo. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved. At concentrations from 10 n m to 1 m m, 5-HT induced concentration-dependent contractions. Significant contractions were not observed with 5-HT1Aagonist 8-OH-DPAT (10(-9)-10(-4)m), 5-HT1Dalphaagonist sumatriptan (10(-9)-10(-4)m), 5-HT2agonist DOI (10(-9)-10(-4)m), 5-HT3agonist 2-methyl 5-HT (10(-9)-10(-3)m) and 5-HT4agonist renzapride (10(-9)-10(-3)m) on the human isolated ureter. On the other side, a 5-HT1-likeagonist 5-CT (10(-9)-10(-3)m) produced contractions on the isolated samples. The Emaxdeveloped by 5-CT was significantly smaller than that of the 5-HT (29% of 5-HT). Methithepin, the less selective 5-HT1/2antagonist (10(-9)-10(-6)m), 5-HT3antagonist, ondansetron (10(-9)-10(-5)m) and 5-HT4antagonist DAU 6285 (10(-8)-10(-6)m) did not antagonise the contractile responses to 5-HT. 10(-7)m ketanserin antagonised 5-HT induced contractile responses in ureteral strips. Additionally, combined administration of 5-HT4antagonist DAU 6285 (10(-6)m) and 5-HT1/2antagonist methithepin (10(-6)m) caused a rightward shift of the CRC of 5-HT yielding pEC50values of 4.68+/-0.15. 5-HT-induced contractile responses that were not abolished by TTX and atropine, thus supporting the suggestion that in the human, the contractile responses to cumulative addition of 5-HT of the ureter are not mediated by excitation of cholinergic neurons. In the present study the receptor mediating the contractile response to 5-HT in the human upper ureter could not be clearly designated 5-HT1-like, 5-HT2, 5-HT3or 5-HT4. This study suggests that contractile response to 5-HT in the upper segments of the human ureter appear to be mediated by an atypical 5-HT receptor subtype.