Effect of norepinephrine on the concentration of adenosine 3',5'-monophosphate of rat pineal gland in organ culture.

Abstract

The in vitro addition of norepinephrine ( 10-4M) to rat pineal glands maintained in organ culture caused about a six-fold increase in the endogenous concentration of adenosine 3′,5′-monophosphate (cyclic 3′,5′-AMP). This increase was evident within 5 min, and the concentration of cyclic 3′,5′-AMP remained elevated for more than 2 hr. Theophylline ( 10-2M), an inhibitor of phosphodiesterase activity, also raised the concentration of cyclic 3′,5′-AMP in pineal glands and markedly enhanced the effects of norepinephrine. The rise of cyclic 3′,5′-AMP induced by norepinephrine or theophylline preceded the elevation of N-acetyltransferase activity and the increased formation of melatonin. The beta adrenergic blocking agent, propranolol, completely inhibited the norepinephrine-induced elevation of cyclic 3′5′-AMP, whereas, the alpha adrenergic drug, phentolamine, was totally ineffective. The time course of the increased concentration of cyclic 3′,5′-AMP in response to norepinephrine was compatible with a theory of a norepinephrine-adenylate cyclasecyclic 3′,5′-AMP dependent mechanism being responsible for changes of the activity of N-acetyltransferase and in the production of melatonin by the pineal gland. (Endocrinology90: 1470, 1972)