Histamine regulation of adenylyl cyclase of enriched rat gastric parietal cells

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Abstract
Rat gastric parietal cells were isolated to 90% or greater purity by discontinuous gradient ultracentrifugation in sucrose-Ficoll. Adenylate cyclase activity was initiated by histamine in the presence of 5''-guanylate imidodiphosphate, but not by pentagastrin or acetylcholine. The concentration of histamine needed for half-maximal activation of adenylate cyclase was 38 .mu.M. The histamine H2-receptor antagonist, metiamide, inhibited histamine (100 .mu.M) activation with a Ki of 0.9 .mu.M. The effects of other histamine agonists and antagonists suggest the presence of H2-type histaminic receptors on parietal cells. Adenylate cyclase activity was also stimulated by isoproterenol, norepinephrine and epinephrine, but not by methoxamine. Half-maximal activation by isoproterenol occurred at 0.5 .mu.M. Propranolol, but not phentolamine, prevented activation by these agents, indicating the presence of .beta.-adrenergic receptors on parietal cells. Prostaglandins E2 stimulated adenylate cyclase of partially purified (30%), but not the enriched (90%), parietal cell populations.