Pharmacological characterization and autoradiographic localization of dopamine receptors in human epicardial arteries.
The pharmacological properties and the anatomical localization of dopamine (DA) D1 and D2 receptor sites were studied in normal samples of the human right coronary and anterior interventricular arteries by assessing the effect of DA on the cyclic AMP generating system and by using combined radioreceptor binding and autoradiographic techniques. DA caused a concentration-dependent accumulation of cyclic AMP in membranes of right and anterior interventricular coronary arteries. This effect was antagonized by the selective D1 receptor antagonist SCH 23390 and by other DA receptor antagonists. D2 receptor responses negatively coupled to cyclic AMP generation were obtained by incubating membranes of coronary arteries with DA together with SCH 23390 or with D2 receptor agonists. This D2 effect was abolished by the selective D2 receptor antagonist (-)-sulpiride. [3H]SCH 23390 was bound to sections of the coronary arteries in a manner consistent with the labeling of D1 sites. Light microscope autoradiography revealed the localization of D1 sites in the medial layer of the coronary arteries. [3H]Spiroperidol, in the presence of ketanserin, was bound to sections of the coronary arteries in a manner consistent with the labeling of D2 sites. D2 receptor sites were located within the adventitia and the adventitial-medial border of the two arteries, and are probably prejunctional in nature. These findings indicate the existence of both D1 and D2 receptor sites in human right and anterior interventricular arteries. Moreover, they suggest that coronary vasodilation induced by DA or DA receptor agonists may be the result of a direct coronary vasodilatory activity.
Amenta
F
F
Dipartimento di Sanità Pubblica e Biologia Cellulare, Università Tor Vergata, Rome, Italy.
Ferrante
F
F
Rossodivita
A
A
Ricci
A
A
D000293:Adolescent; D001158:Arteries / Q000737:chemistry; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D003331:Coronary Vessels / Q000737:chemistry*; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D017447:Receptors, Dopamine D1 / Q000032:analysis*; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D000242:Cyclic AMP; D004298:Dopamine