Characterization of serotonin receptors in isolated rat intramyocardial coronary artery.
The purpose of the present study was to characterize the receptor subtypes that mediate serotonin (5-HT)-induced contraction in isolated rat intramyocardial coronary artery. In coronary artery with and without endothelium, only 5-HT and alpha-methylserotonin maleate (5-HT2 agonist) elicited equipotent concentration-dependent contractions. The EC50 values for 5-HT and alpha-methylserotonin maleate in endothelium-intact arteries were 4.7 x 10(-7) and 4.5 x 10(-7) M, respectively, whereas in endothelium-denuded arteries they were 2.8 x 10(-7) and 1.9 x 10(-7) M, respectively. The other subtype agonists, such as (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (5-HT1A agonist), 1-(3-chlorophenyl)piperazine dihydrochloride and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (5-HT1B) and 2-methyl-serotonin maleate (5-HT3), only elicited a small percentage of the maximum contraction to 5-HT. In prostaglandin F2 alpha-precontracted coronary arteries with intact endothelium or denuded of endothelium, the addition of 5-HT resulted in a further increase in tension. No relaxation was observed with 5-HT up to 1 x 10(-5) M. The contraction induced by 5-HT in artery both with and without endothelium was inhibited by ketanserin (5-HT2 antagonist) but not by l-propranolol (5-HT1 antagonist) nor by 3-tropanyl-indole-3,5-dichlorobenzoate (5-HT3 antagonist). Ketanserin, the selective 5-HT2 antagonist, effectively antagonized 5-HT-induced contraction by shifting the 5-HT response curve to the right without inhibiting the maximal response in both endothelium-intact and -denuded arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Lai
F M
FM
Department of Cardiovascular Biology, American Cyanamid Co., Lederle Laboratories, Pearl River, New York.
Tanikella
T
T
Cervoni
P
P
D000818:Animals; D003331:Coronary Vessels / Q000648:ultrastructure*; D015237:Dinoprost / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology / Q000648:ultrastructure; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; C042390:alpha-methylserotonin; D012701:Serotonin; D007650:Ketanserin; D011433:Propranolol; D015237:Dinoprost; C042253:bemesetron