Comparison of the response to 5-carboxamidotryptamine and serotonin in isolated human, monkey and dog coronary arteries.
In isolated dog coronary arteries, serotonin (5-HT) produced a contraction, whereas 5-carboxamidotryptamine (5-CT), a serotonergic 5-HT1-like receptor agonist, mainly relaxed the arteries, and the contraction, if any, was slight. Human and Japanese monkey coronary artery strips responded to these amines only with contractions, the magnitude being markedly greater than that of serotonin-induced contractions in the dog arteries. Removal of endothelium slightly potentiated the serotonin-induced contraction and abolished the relaxation by 5-CT or reversed it to a contraction in the dog arteries; however, contractions elicited by serotonin and 5-CT in the human and monkey arteries were not influenced. Treatment with 10(-7) M 5-CT suppressed the contraction by serotonin in the dog arteries but did not alter the response of the monkey arteries. Relaxation of the dog arteries with endothelium caused by 5-CT and contraction of the arteries denuded of endothelium were not inhibited by ketanserin but they were by methysergide. 5-CT-induced contractions of human and monkey coronary arteries were attenuated by ketanserin and methysergide, although the inhibition was less with the 5-HT2 antagonist. Ketanserin inhibited the contraction by serotonin to a greater extent than the 5-CT-induced contraction in the monkey arteries. It may be concluded that 5-CT stimulates 5-HT1-like and 5-HT2 receptor subtypes in smooth muscle of human and monkey epicardial coronary arteries but acts exclusively on 5-HT1-like receptors in endothelium and smooth muscle of dog coronary arteries. Serotonin contracts the primate arteries, possibly by predominant activation of 5-HT2 over 5-HT1-like receptors.
Toda
N
N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D008251:Macaca; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*
D012702:Serotonin Antagonists; D012701:Serotonin; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D008784:Methysergide