Divalent cation-induced interconversion of hepatic angiotensin receptor subtypes.

The effects of divalent cations on the hepatic angiotensin receptor have been investigated using radioligand binding methods. With a plasma membrane-enriched fraction from rat liver, a total binding capacity for angiotensin peptides of 0.5 pmol/mg of membrane protein was observed. In the absence of divalent cations, almost all of these sites showed low affinity (KD, 11.25 nM) for angiotensin II. In the presence of Ca2+, there was a concentration-dependent increase in the proportion of sites with high affinity (KD, 0.94 nM) for angiotensin II. Mg2+, Sr2+, and Ba2+ were less effective in this respect, although Mg2+ also modified affinity of the high affinity subtype. Monovalent cations (Na+, Cs+, and K+) had little effect on angiotensin binding. Both receptor subtypes showed high and approximately equal affinity for sarcosine1-analogues of angiotensin II and 10-fold lower and equal affinity or Ile7-angiotensin III. The low affinity subtype appeared to be more sensitive to N-terminal deletions in the peptide. Interconversion of receptor subtypes could be prevented by 5'-guanylylimidodiphosphate, La3+, diltiazem, and verapamil. The results show that the hepatic angiotensin receptor can exist in high and low affinity states in vitro and that the proportion in each state can be modified by divalent cations, guanine nucleotides, and some Ca2+ antagonist drugs.