SIMILARITIES AND DIFFERENCES IN THE NOREPINEPHRINE-AND SODIUM FLUORIDE-SENSITIVE ADENYL CYCLASE SYSTEM

¹ Departments of Pharmacology and Neurology, College of Physicians and Surgeons of Columbia University, New York, New York

Adenyl cyclase activity of rat pineal gland was determined by measuring the rate of formation of radioactive 3',5'-adenosine monophosphate from C¹⁴-labeled adenosine triphosphate. Norepinephrine and sodium fluoride added in vitro markedly increased adenyl cyclase activity of pineal homogenates by a mechanism unrelated to inhibition of phosphodiesterase or adenosine triphosphatase. These two stimulants were used to determine whether there are different sites on the pineal adenyl cyclase system with which compounds may act to increase enzymic activity. Several similarities in the norepinephrine-and sodium fluoridesensitive adenyl cyclase system were found. For example, freezing or allowing pineal homogenates to stand at 30°C reduced the response of the enzyme to norepinephrine and to sodium fluoride by about the same degree and at a similar rate. The pH optimum of adenyl cycla. se was the same for the two stimulants. The in vitro addition of phentolamine slightly increased the response to both compounds. On the other hand, evidence was found for differences in the sites of action. The activation of adenyl cyclase by maximally effective concentrations of sodium fluoride was increased by the addition of norepinephrine. Moreover, the beta adrenergic blocking drugs propranolol and dichloroisoproterenol inhibited the response to norepinephrine; however, propranolol had no effect on the response to sodium fluoride, and dichloroisoproterenol increased the fluoride response. Thus, the results suggest that, in the pineal gland, the adenyl cyclase systems that respond to norepinephrine and to sodium fluoride have many characteristics in common, but the specific sites at which these compounds interact to elicit their effects are different.