Protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor in rat parietal cells.

The action of protein kinase C on the stimulation of adenylate cyclase activity by the histamine H2 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 microM). This effect was related to the concentration of TPA. TPA (100 nM) enhanced the stimulation of adenylate cyclase activity by forskolin (100 microM) but had no effect on the stimulation by NaF (10 mM). In conclusion, protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor. This action could be mediated by changes in the number of affinity of histamine H2 receptors or in the coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit Gs.