Regulation of membrane histamine H1-receptor binding sites by guanine nucleotides, mono- and divalent cations.

Agonist interaction with histamine H1-receptor in [3H] mepyramine bovine aortic membranes labeled with [3H] mepyramine is selectively regulated by cations and guanine nucleotides. GTP and his nonhydrolisable analog Gpp(NH)p' markedly decrease histamine affinity for [3H] mepyramine binding sites. The effect of GTP is reversed in the presence of divalent cation, magnesium. Calcium and sodium ions have little effect on histamine binding whereas magnesium ions decrease the affinity of histamine for the radioantagonist binding sites about tenfold. GTP has little effect on [3H] mepyramine binding and the interaction of H1-antagonist triprolidine with histamine H1-receptors. The above results indicate that the effect of guanine nucleotides, mono and divalent cations involves the effect on membrane signal transducing mechanism probably GTP-binding protein(s) cation regulatory site(s) rather than receptor binding site directly.