Molecular Pharmacology, Vol 9, 184-190, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

Role of the Beta Adrenergic Receptor in the Elevation of Adenosine Cyclic 3',5'-Monophosphate and Induction of Serotonin N-Acetyltransferase in Rat Pineal Glands

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland 20014

The adenosine cyclic-3',5' monophosphate level in rat pineal gland is elevated 15-fold 2 min after intravenous injection of l-isoproterenol and returns to the baseline level after 30 min. Pineal serotonin N-acetyltransferase (EC 2.3.1.5) activity rises after 1 hr of lag phase and increases 70-100-fold 3 hr after injection of l-isoproterenol. Prior treatment with l-propranolol, a beta adrenergic blocking agent, blocks both the elevation of cyclic AMP and the increase in N-acetyltransferase activity by l-isoproterenol. When l-propranolol is injected after the cyclic AMP level has returned to the baseline and before N-acetyltransferase activity starts to rise, the increase in enzyme activity is blocked. l-Propranolol injected after N-acetyltransferase activity has reached its maximum level causes a precipitous fall in N-acetyltransferase activity, to 5% of the initial level in 15 min, whereas d-propranolol does not decrease enzyme activity. Other beta adrenergic blocking agents, practolol and pronethalol, also cause a rapid disappearance of N-acetyltransferase activity. Cycloheximide, an inhibitor of protein synthesis, blocks the increase in N-acetyltransferase activity when administered 30 min before or 1 hr after the injection of l-isoproterenol and before enzyme activity starts to increase. If cycloheximide is injected after the maximum level of N-acetyltransferase activity has been reached, there is no decrease in enzyme activity over 15 min. When rat pineal with a high level of N-acetyltransferase activity is incubated in vitro, there is no change in enzyme activity. In the presence of either l-propranolol or dichloroisoproterenol, however, N-acetyltransferase activity disappears very rapidly. These observations suggest that the maintenance of the high level of N-acetyltransferase activity requires continuous stimulation of the beta adrenergic receptor on the pineal cell, regardless of the level of cyclic AMP.

Note:
ACKNOWLEDGMENT The author thanks Dr. Julius Axelrod for his helpful suggestions and encouragement throughout this study.

This article has been cited by other articles:

				S.A. Checkley and S.B.G. Park The psychopharmacology of the human pineal J Psychopharmacol, January 1, 1987; 1(2): 109 - 125. [Abstract] [PDF]

				T Deguchi Circadian rhythm of serotonin N-acetyltransferase activity in organ culture of chicken pineal gland Science, March 23, 1979; 203(4386): 1245 - 1247. [Abstract] [PDF]

				D. Klein, M. Buda, C. Kapoor, and G Krishna Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff" Science, January 20, 1978; 199(4326): 309 - 311. [Abstract] [PDF]

				M Zatz and R. O'Dea Efflux of cyclic nucleotides from rat pineal: release of guanosine 3',5'-monophosphate from sympathetic nerve endings Science, July 8, 1977; 197(4299): 174 - 176. [Abstract] [PDF]

				K. Minneman and L. Iversen Cholera toxin induces pineal enzymes in culture Science, May 21, 1976; 192(4241): 803 - 805. [Abstract] [PDF]

				D. McMahon Chemical Messengers in Development: A Hypothesis Science, September 20, 1974; 185(4156): 1012 - 1021. [Abstract] [PDF]

				J. Axelrod The Pineal Gland: A Neurochemical Transducer Science, June 28, 1974; 184(4144): 1341 - 1348. [PDF]