Effects of ketanserin and DOI on spontaneous and 5‐HT‐evoked peristalsis of the pig ureter in vivo

The influence of 5‐hydroxytryptamine (5‐HT) receptor agonists and antagonists on the ureter motility was investigated in vivo on intact ureters of anaesthetized pigs. Drugs were administered intravenously or topically. 5‐HT induced a dose‐dependent increase in the frequency of ureter contractions in anaesthetized pigs when given intravenously (0.0001 – 1 mg kg −1 ; ED 50 0.066 mg kg −1 ) or topically (0.001 – 1 mg ml −1 ; EC 50 0.043 mg ml −1 ). Significant increases in heart rate and blood pressure were observed when the drug was given intravenously but not topically. The 5‐HT 2A agonist, DOI (1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane) increased the frequency of ureteral contractions in a dose‐dependent manner (1 – 300 μg kg −1 i.v.). Calculation of ED 50 indicated this compound to be about 1.5 times more potent with an efficacy of 23% compared to 5‐HT. The 5‐HT 2A/2C antagonist, ketanserin (0.5 mg kg −1 ) and the 5‐HT 2C antagonist, methysergide (1 mg kg −1 ) antagonized the 5‐HT‐induced ureter peristalsis when given intravenously. Contraction amplitude, blood pressure and heart rate were not affected by the antagonists. Intravenous (0.0001 – 1 mg kg −1 ) and topical (0.0001 – 1 μg ml −1 ) ketanserin significantly decreased the frequency of spontaneous ureteral contractions to about 30% of controls, which could be partly reversed by 5‐HT (0.3 mg kg −1 i.v.). The contraction amplitude, contractions of the contralateral, saline perfused ureter, heart rate and mean arterial blood pressure were not affected. Thus, contractility of porcine ureter is mediated by 5‐HT 2 receptors. Their antagonists ketanserin and methysergide seem to be promising drugs for treatment of acute ureteric colic or in preparing the ureter for ureteroscopy.British Journal of Pharmacology (2002) 135 , 1026–1032; doi: 10.1038/sj.bjp.0704536