Proto-oncogene fos (c-fos) expression in the heart

Administration of the beta-adrenergic agonist isoproterenol led to a marked rapid increase in the steady-state level of c-fos mRNA in the heart of mice, rats, and Syrian hamsters. Stimulation of c-fos expression by isoproterenol was inhibited by the beta-adrenergic antagonist propranolol. An increase in Ca2+ influx through voltage-dependent calcium channels is probably not required for the activation of the c-fos gene by isoproterenol since the calcium channel blockers verapamil, nifedipine, and diltiazem had no effect on the induction of c-fos by the drug. In the heart of the rat, c-fos expression was also stimulated by the alpha-adrenergic agonist phenylephrine, histamine, and prostaglandin E1. The histamine-induced expression of the c-fos gene was blocked by the histamine H1-receptor antagonist pyrilamine but not by H2-receptor antagonists ranitidine and cimetidine. It is concluded that in the heart, hormones which increase cAMP and cytosolic Ca2+, such as beta-adrenergic agonists and prostaglandin E1, and/or stimulate the turnover of inositol phospholipids, such as alpha-adrenergic agonists and histamine H1-receptor agonists, regulate c-fos gene expression. The fos protein is likely to play a role in the mechanisms of neurotransmitters and hormones that modulate the functioning of the heart and of cardiac hypertrophy, degeneration and necrosis.