Histamine regulation of adenylyl cyclase of enriched rat gastric parietal cells.

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