PHARMACOLOGICAL ANALYSIS OF 5-HYDROXYTRYPTAMINE EFFECTS ON HUMAN ISOLATED URETER

• Published in: Pharmacological research Vol. 39; no. 6; pp. 487 - 491
• Main Authors: GİDENER, SEDEF, GÜMÜŞTEKİN, MUKADDES, KIRKALI, ZIYA
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.1999
• Subjects: Adult; Aged; Dose-Response Relationship, Drug; Female; human, ureter, serotonin, in vitro; Humans; In Vitro Techniques; Male; Middle Aged; Muscle Contraction - drug effects; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Receptors, Serotonin - drug effects; Receptors, Serotonin, 5-HT1; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin - analogs & derivatives; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Ureter - drug effects; Ureter - physiology; human, ureter, serotonin, in vitro
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.1999.0469

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 (10−9–10−4m), 5-HT1Dαagonist 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-HT1-likeagonist 5-CT (10−9–10−3m) 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 (10−9–10−6m), 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-HT1/2antagonist 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-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.1999 Academic Press@p$hr