PROTEIN-KINASE-C INHIBITS STIMULATION OF ADENYLATE-CYCLASE BY THE HISTAMINE H-2-RECEPTOR IN RAT PARIETAL-CELLS

The action of protein kinase C on the stimulation of adenylate cyclase activity by the histamine H-2 receptor was investigated in rat parietal cells. Protein kinase C was activated by preincubating cells with 12-O-tetradecanoylphorbol 13-acetate (TPA), and adenylate cyclase activity was measured in sonicated extracts. TPA (100 nM) inhibited adenylate cyclase activity stimulated by histamine (100 nM-500 muM). This effect was related to the concentration of TPA. TPA (100 nM) enhanced the stimulation of adenylate cyclase activity by forskolin (100 muM) but had no effect on the stimulation by NaF (10 mM). In conclusion, protein kinase C inhibits stimulation of adenylate cyclase by the histamine H-2 receptor. This action could be mediated by changes in the number or affinity of histamine H-2 receptors or in the coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit Gs.