Abstract

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)