Pharmacological Analysis of 5-Hydroxytryptamine Effects on Human Isolated Ureter

Author： GİdenER S. GÜMÜŞTEKİN M. Kirkali Z.

ISSN： 1043-6618

Source： Pharmacological Research, Vol.39, Iss.6, 1999-06, pp. : 487-491

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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-HT_1Aagonist 8-OH-DPAT (10^-9–10^-4m), 5-HT_1Dagonist sumatriptan (10^-9–10^-4m), 5-HT₂agonist DOI (10^-9–10^-4m), 5-HT₃agonist 2-methyl 5-HT (10^-9–10^-3m) and 5-HT₄agonist renzapride (10^-9–10^-3m) on the human isolated ureter. On the other side, a 5-HT_1-likeagonist 5-CT (10^-9–10^-3m) produced contractions on the isolated samples. The E_maxdeveloped by 5-CT was significantly smaller than that of the 5-HT (29% of 5-HT). Methithepin, the less selective 5-HT_1/2antagonist (10^-9–10^-6m), 5-HT₃antagonist, ondansetron (10^-9–10^-5m) and 5-HT₄antagonist DAU 6285 (10^-8–10^-6m) did not antagonise the contractile responses to 5-HT. 10^-7m ketanserin antagonised 5-HT induced contractile responses in ureteral strips. Additionally, combined administration of 5-HT₄antagonist DAU 6285 (10^-6m) and 5-HT_1/2antagonist methithepin (10^-6m) 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-HT_1-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.1999 Academic Press@p$hr