Possible regulation of ornithine decarboxylase activity in the adrenal medulla of the rat by a cAMP-dependent mechanism

Abstract

Ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis, may be controlled by a cAMP-dependent mechanism. This hypothesis was investigated in the adrenal medulla of the rat. Exposure of rats to cold (4°, 2 hr) leads to increased cholinergic nerve transmission and to a 10- to 20-fold increase in cAMP levels in the medulla within 30 min. The cAMP level returned to normal within 2 hr of the initiation of cold exposure. Ornithine decarboxylase activity was elevated within 1 hr of cold exposure and by 4 hr was increased 10- to 20-fold. We also studied the effects of various drugs which were agonists and antagonists of the cAMP response to cold exposure in the medulla. Aminophylline (200 μmoles/kg), an inhibitor of phosphodiesterase activity, caused a large, rapid increase in the cAMP level followed by an increase in ornithine decarboxylase activity similar to that after cold exposure. Injection of a cholinomimetic drug, carbamylcholine (4.1 μmoles/kg), caused a 10- to 15-fold increase in cAMP within 20 min and a 10-fold elevation in ornithine decarboxylase activity within 2.5 hr. Pretreatment of the rat with the nicotinic receptor antagonist, mecamylamine (15 μmoles/kg), greatly reduced the carbamylcholine-induced rise in both cAMP levels and ornithine decarboxylase activity. Mecamylamine administered alone did not alter either cAMP levels or ornithine decarboxylase activity. Administration of reserpine (16 μmoles/kg) also resulted in an early rise in cAMP concentration in the adrenal medulla and a concomitant increase of ornithine decarboxylase activity. Cyclic AMP has been postulated to exert its effect on cellular metabolism via the activation of a cAMP-dependent protein kinase. Varying doses of reserpine from 1.6 to 16 μmoles/kg yielded a 1:1 relationship between the degree of activation of cAMP-dependent protein kinase(s) and the induction of ornithine decarboxylase. We feel that evidence from this and other laboratories supports the hypothesis that ornithine decarboxylase may be controlled by cAMP-dependent protein kinase(s).