Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. II.

The effects of histamine on heart cAMP-dependent protein kinase activity, cAMP levels, phosphorylase activity, and contractile force was investigated in the perfused guinea pig heart. To accurately determine the protein kinase activity ratio in guinea pig heart, it was necessary to measure kinase activity in whole homogenates immediately after homogenization of the tissue. Histamine produced a rapid dose-dependent increase in cAMP and the protein kinase activity ratio followed by increased in contractile force and phosphorylase activity. There was a good correlation between the degree of protein kinase activation and the increase in phosphorylase and force. The beta-adrenergic blocking agent propranolol did not reduce the effects of histamine, but metiamide, a potent H2-receptor antagonist, greatly attenuated all the effects of histamine. The data support the hypothesis that increases in heart cAMP-dependent protein kinase activity produce corresponding increases in contractile force and phosphorylase activity.