Pharmacologic Receptor Activity of Rabbit Aorta

Abstract

N -ethylmaleimide (NEM), an alkylating agent that covalently binds sulfhydryl groups, and dithiothreitol (DTT, Cleland's reagent), which reduces disulfide bridges to sulfhydryl groups, affected drug-induced contractions of rabbit aorta. NEM depressed aortic responses to potassium chloride (KCl), norepinephrine, serotonin, histamine, and angiotensin II. This action was attributed to an interaction of NEM with sulfhydryl groups vital to either the membrane function or the contractile apparatus. DTT had minimal effects on responses to KCl, norepinephrine, and serotonin; it potentiated aortic contractions produced by histamine and abolished responses to angiotensin II. Enhancement of the histamine response by DTT was not accompanied by an effect on the histamine-metabolizing enzymes or by an alteration in the K B and pA 2 values for pyrilamine. The results suggest that a disulfide bridge plays a prominent role in both histamine and angiotensin receptor activity of rabbit aorta. With regard to the histamine receptor system, two possibilities exist: (1) reduction of a disulfide bridge at some vital point increases receptor activity or (2) the histamine receptor system, normally in a reduced state, is oxidized in the artificial environment of the tissue bath and needs to be reduced to regain full activity.