Differential effects of cations and guanyl nucleotides on agonist and antagonist binding to rat adrenal and uterine angiotensin II receptors

Abstract

The effects of various modulators (cations, Gpp(NH)p) of hormone-receptor interaction were tested on agonist ([ 125I]angiotensin II) and antagonist ( 125I-[Sar 1,Ala 8]angiotensin II) binding to membrane particles from the rat adrenal zona glomerulosa and uterine smooth muscle. The two radioiodinated peptides labeled the same population of binding sites. Sodium ion (140 mM) induced a 2 fold increase in the affinity of adrenal angiotensin II receptors for the agonist (K a = 2.15 nM −1, vs. 1.01 nM −1 for controls), but decreased antagonist binding by reducing the number of available receptors by up to 50% in both adrenal and uterine membrane particles. Potassium ion only inhibited antagonist binding. Calcium and magnesium ions (0–10 mM) increased agonist binding and decreased antagonist binding to adrenal and uterine angiotensin II receptors, an effect mediated by changes in both affinity and number of receptors for the two peptides. The non-hydrolyzable GTP analog, Gpp(NH)p (10 −9 - 10 −4 M) decreased the affinity of angiotensin II receptors for the agonist by up to 50%, but did not affect antagonist binding to the receptor. Thus, there were marked differences in the sensitivity of agonist and antagonist peptides of angiotensin II to the modulatory effect of cations and guanyl nucleotides on ligand-receptor interaction. It is suggested that these differences may be important in determining the activatory/inhibitory properties of angiotensin peptides.