RGS 2 and RGS 4 Differentially Modulate G Protein Coupled Receptor Signaling in the Mouse Aorta

Abstract

Regulator of G protein signaling (RGS) proteins terminate G protein signaling by enhancing the rate of GTP hydrolysis. We compared the ability of RGS 2 and RGS 4 to modulate the actions of several G protein coupled receptor agonists in isolated mouse aortic rings. Genetic deletion of either RGS 2 or RGS 4 significantly enhanced the efficacy of phenylephrine‐induced contraction but had no effect on the potency of phenylephrine. The serotonin‐induced contractile response was unaffected by deletion of RGS 2, but the efficacy of serotonin was significantly attenuated by deletion of RGS 4. This effect of RGS 4 deletion was reversed by L‐nitroargenine methyl ester or by denuding the aorta. Deletion of RGS 2 or RGS 4 had no effect on the efficacy or potency of carbachol‐induced aortic relaxation. Angiotensin II and clonidine produced no aortic contraction irrespective of the presence of RGS 2 or RGS 4. These data demonstrate that RGS 2 and RGS 4 differentially modulate aortic responses induced by phenylephrine, serotonin, and carbachol. Furthermore, RGS 4 modulates serotonin‐induced contraction through a mechanism that is dependent upon the presence of an intact endothelium and functional nitric oxide synthase. (This work was supported by GM39561).