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

K M Baker, H A Singer
1988 Circulation Research  
Angiotensin II elicits a receptor-mediated positive inotropic response in cardiac tissue from most mammalian species by activating voltage-sensitive slow Ca 2+ 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, '"I-angiotensin II binding sites that have the characteristics of a membrane receptor were identified in ventricular (myocardial) and
more » ... l membrane preparations from guinea pigs. In ventricles, saturation-binding data yielded an optimal At to a two-site model with a high-affinity site Kj, = 3.6 ± 0.7 nM and a low-affinity site K^ = 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 K dl = 1.6 nM and a low-affinity site 1^ = 300 nM and capacities of 145 and 752 fmol/mg protein, respectively. The ventricular binding of '"I-angiotensin II was stimulated -twofold in the presence of the divalent cations calcium and magnesium (10 mM). Nonhydrotyzable analogues of guanosine triphosphate increased the dissociation rate of the bound '"I-angiotensin II and decreased hormone binding to the receptor at equilibrium. Competition for '"I-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 [Sar 1 ,Ile*]angiotensin II. This species may provide the opportunity to study the angiotensin H-induced phosphoinositide response and potential physiological sequelae (i.e., hypertrophy) in isolation from Ca 2+ channel activation and resultant mechanical responses. (Circulation Research 1988;62:896-904)
doi:10.1161/01.res.62.5.896 pmid:3359576 fatcat:w422dywkczbmpjde2sa44girmq