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 (p[NH]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 p[NH]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 p[NH]ppG plus histamine stimulated, rather than inhibited, Ca2(+)-ATPase activity. We concluded that p[NH]ppG and histamine acted together to increase Ca2+ permeability. In support of this, p[NH]ppG accelerated efflux of Ca2+ from passively loaded vesicles sonicated with, but not without, histamine. The effect of p[NH]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 p[NH]ppG increased the permeability of the plasmalemma vesicles and may thus model the process of receptor-mediated Ca2+ entry into intact cells.
Blayney
L M
LM
Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Newby
A C
AC
D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure*; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology
D006150:Guanine Nucleotides; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D006632:Histamine; D000252:Calcium-Transporting ATPases; D002118:Calcium