Histamine and a guanine nucleotide increase calcium permeability in pig aortic microsomal fractions.

ATP-dependent Ca2+ accumulation was measured in pig aortic microsomal fractions containing plasmalemma and endoplasmic reticulum. In vesicles sonicated with histamine, to allow access to internally located receptor sites, guanosine 5'-beta gamma-imido]triphosphate (pNH]ppG), added to activate externally located guanine-nucleotide-transducing proteins, caused a concentration-dependent decrease in steady-state Ca2+ accumulation that was reversed by guanosine 5'-beta-thio]diphosphate. In the presence of pNH]ppG, sonication with histamine produced a concentration-dependent inhibition of Ca2+ accumulation that could be antagonized by the H1 antagonist mepyramine, but not by the H2 antagonist cimetidine. The inhibition of steady-state Ca2+ accumulation could have resulted from an inhibition of ATP-dependent Ca2+ uptake or a stimulation of Ca2+ release. We observed, however, that pNH]ppG plus histamine stimulated, rather than inhibited, Ca2(+)-ATPase activity. We concluded that pNH]ppG and histamine acted together to increase Ca2+ permeability. In support of this, pNH]ppG accelerated efflux of Ca2+ from passively loaded vesicles sonicated with, but not without, histamine. The effect of pNH]ppG was unlikely to be due to Ins(1,4,5)P3 (and hence release from endoplasmic-reticulum vesicles), since addition of Ins(1,4,5)P3 to vesicles sonicated with histamine did not alter steady-state Ca2+ accumulation. Our results therefore suggest that histamine and pNH]ppG increased the permeability of the plasmalemma vesicles and may thus model the process of receptor-mediated Ca2+ entry into intact cells.