Effects of ketanserin and DOI on spontaneous and 5-HT-evoked peristalsis of the pig ureter in vivo.
1. 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. 2. 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. 3. 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 microg 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. 4. 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. 5. Intravenous (0.0001-1 mg kg(-1)) and topical (0.0001-1 microg 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. 6. 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.
Hauser
D S
DS
Institute of Veterinary Pharmacology, University of Bern, 3012 Bern, Switzerland.
Mevissen
M
M
Weiss
R
R
Portier
C J
CJ
Scholtysik
G
G
Studer
U E
UE
Danuser
H
H
D000818:Animals; D005260:Female; D007215:Indophenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013552:Swine; D014513:Ureter / Q000187:drug effects* / Q000502:physiology
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D012701:Serotonin; D007215:Indophenol; D007650:Ketanserin; D008784:Methysergide