Receptors for 5-hydroxytryptamine in rabbit blood vessels: activation of alpha adrenoceptors in rabbit thoracic aorta

RE Purdy, DL Murray and GL Stupecky

Experiments were carried out to identify the receptors mediating the contraction of the rabbit thoracic aorta to 5-hydroxytryptamine (5-HT). Isolated aortic rings were mounted in tissue baths for the measurement of isometric contraction and 5-HT dose-response curves were obtained in the presence and absence of receptor antagonists. Prazosin, 1 X 10(-7) M, or 30-min pretreatment with 1 X 10(-5) M benextramine had no effect on the contractile response of aorta to 5-HT up to 1 X 10(-5) M, whereas 2 brom-D-lysergic acid diethylamide, 1 X 10(-7) M, shifted the 5-HT dose-response curve far to the right. Alpha receptor blockade with either prazosin or benextramine in the presence of 2 brom-D-lysergic acid diethylamide produced a greater blockade than that caused by 2 brom-D-lysergic acid diethylamide alone. When 5-HT dose-response curves were extended to 1 X 10(-3) M, three phases were identified. The first, a dose-related contraction, was mediated exclusively by serotonergic receptors. The second, a relaxation to approximately 40% of maximum, occurred at 1 X 10(-5) M and appeared to result from the rapid development of tachyphylaxis. The third phase was a dose-related contraction to concentrations of 5-HT above 1 X 10(-5) M and was inhibited by either prazosin or pretreatment with benextramine. Similar results were obtained in aortic rings from reserpine-pretreated rabbits. It is concluded that the contractile response to concentrations of 5-HT below 1 X 10(-5) M is mediated exclusively by serotonergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 240, Issue 2, pp. 535-541, 02/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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