Inhibition of plasma cholinesterase prevents the dopamine DA-1 receptor mediated renal vasodilation produced by ibopamine.
We have studied the dopamine DA-1 receptor mediated renal vasodilator response of the inotropic pro-drug, ibopamine, the diisobutyrate ester of epinine. In anesthetized dogs pretreated with phenoxybenzamine and propranolol to eliminate alpha- and beta-adrenoceptor mediated responses, respectively, ibopamine and epinine produced dose-dependent renal vasodilation. Treatment of animals with the cholinesterase inhibitor, physostigmine, markedly inhibited the renal vasodilation produced by ibopamine, but had no effect on the renal vasodilator response of epinine. We conclude that hydrolysis of ibopamine by plasma cholinesterase to yield epinine is necessary for the production of the dopamine DA-1 receptor mediated renal vasodilator response to ibopamine.
Nichols
A J
AJ
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939.
Shebuski
R J
RJ
Ruffolo
R R
RR
D000818:Animals; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000097:blood; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives*; D005260:Female; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D011954:Receptors, Dopamine; D014665:Vasodilator Agents; C023487:ibopamine; D002802:Cholinesterases; D003846:Deoxyepinephrine; D004298:Dopamine