Anatomical localization of the binding and functional characterization of responses to dopexamine hydrochloride in the rat mesenteric vasculature.
Dopamine receptors of the DA1 subtype have been identified in mesenteric blood vessels, stimulation of which leads to vasodilation. In this study, we have determined the anatomical localization of dopexamine-hydrochloride-binding sites and carried out functional characterization of responses to this DA1-receptor and beta 2-adrenoceptor agonist in rat mesenteric vasculature. Autoradiographic studies showed the presence of [3H]-dopexamine-binding sites in all the different layers of the mesenteric artery. The DA1 receptor antagonist, SCH 23390 (IC50 = 4.9 mumol/l), and the beta-adrenoceptor antagonist, propranolol (IC50 = 6.0 mumol/l), inhibited the binding of dopexamine. The inhibitory effect of these compounds on dopexamine binding was selective for different regions of the mesenteric artery. Also, dopexamine produced concentration-related increases in cAMP formation in membrane particles from superior mesenteric artery and its main branches. The presence of both SCH 23390 and propranolol was required to completely abolish dopexamine-induced increases in cAMP formation. In functional studies, dopexamine (1 and 3 micrograms/kg/min) produced dose-related increases in mesenteric blood flow (23 and 38%, respectively) which were accompanied by concomitant decreases in the calculated mesenteric vascular resistance. As seen with increases in cAMP, the vascular responses to dopexamine could be completely abolished only by prior treatment with both SCH 23390 and propranolol. These results suggest that in mesenteric vasculature of rat dopexamine binds primarily to DA1 receptors and beta 2-adrenoceptors. The activation of these receptors by dopexamine leads to vasodilation which is mediated by an increase in the intracellular levels of cAMP.
Dipartimento di Sanità Pubblica e Biologia Cellulare, Università Tor Vergata, Roma, Italia.
F
F
Amenta
A
A
Ricci
P
P
Napoleone
S J
SJ
Vyas
M F
MF
Lokhandwala
D000262:Adenylyl Cyclases / Q000378:metabolism; D000322:Adrenergic Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D014316:Tritium
D000322:Adrenergic Agonists; D011954:Receptors, Dopamine; D014316:Tritium; C046318:dopexamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004298:Dopamine