Identification and characterization of guinea pig angiotensin II ventricular and atrial receptors: coupling to inositol phosphate production.

Abstract

Angiotensin II elicits a receptor-mediated positive inotropic response in cardiac tissue from most mammalian species by activating voltage-sensitive slow Ca2+ channels. In the guinea pig, we confirm there is no in vitro contractile force development in bioassay systems using isolated hearts or left atrial tissue in response to angiotensin peptides. However, 125I-angiotensin II binding sites that have the characteristics of a membrane receptor were identified in ventricular (myocardial) and atrial membrane preparations from guinea pigs. In ventricles, saturation-binding data yielded an optimal fit to a two-site model with a high-affinity site Kd1 = 3.6 +/- 0.7 nM and a low-affinity site Kd2 = 433 +/- 126 nM and binding capacities of 66 +/- 10 and 821 +/- 49 fmol/mg protein, respectively. In atria, saturation binding data yielded an optimal fit to a two-site model with a high-affinity site Kd1 = 1.6 nM and a low-affinity site Kd2 = 300 nM and capacities of 145 and 752 fmol/mg protein, respectively. The ventricular binding of 125I-angiotensin II was stimulated approximately twofold in the presence of the divalent cations calcium and magnesium (10 mM). Nonhydrolyzable analogues of guanosine triphosphate increased the dissociation rate of the bound 125I-angiotensin II and decreased hormone binding to the receptor at equilibrium. Competition for 125I-angiotensin II binding by an agonist-antagonist analogue series correlated with previous studies obtained in the rabbit, a mammal in which inotropic responses to angiotensin II were demonstrated. The data indicate the presence of angiotensin II myocardial and atrial receptors and a G-type coupling protein in guinea pig. Although this species lacks an inotropic response to angiotensin peptides, there is a dose-dependent increase in inositol-1-phosphate production in response to angiotensin II, and this response is blocked by the selective angiotensin II antagonist [Sar1,Ile8]angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)