Abstract

Adenyl cyclase activity of rat pineal gland homogenates was assayed in vitro by measuring the rate of formation of radioactive cyclic 3', 5'-adenosine monophosphate (cyclic 3', 5'-AMP) from its C¹⁴-labeled precursor, adenosine triphosphate. Enzyme activity was increased up to 3-fold by the addition of l-norepinephrine. Cyclic 3', 5'-AMP formation was also enhanced by l-epinephrine and l-isoproterenol, but not by d-norepinephrine, dl-dihydroxymandelic acid, dl-normetanephrine, dopamine, tyramine, d-amphetamine or l-phenylephrine. Serotonin and histamine, which are present in the pineal gland and have been shown to increase cyclic 3', 5'-AMP formation in other tissues, did not stimulate pineal adenyl cyclase. Similarly, the polypeptides, glucagon, adrenocorticotropic hormone and luteinizing hormone, which enhance the accumulation of the cyclic nucleotide in liver, adrenal cortex and corpus luteum, respectively, failed to stimulate adenyl cyclase of the pineal. Drugs such as guanethidine, cocaine and desmethylimipramine, which alter sympathetic responses by an action at adrenergic nerve endings, also failed to influence pineal adenyl cyclase activity. On the other hand, the beta adrenergic blocking agents, propranolol and dichloroisoproterenol, which affect beta adrenergic receptors, antagonized the norepinephrine-induced stimulation of enzyme activity. The alpha blockers, phenoxybenzamine and phentolamine, were considerably less effective in this regard. Thus, the results of these studies indicate that adenyl cyclase of rat pineal responds to specific adrenergic and adrenolytic drugs in a manner similar to that of a postjunctional beta adrenergic receptor.