RT Journal Article
SR Electronic
T1 Role of the <em>Beta</em> Adrenergic Receptor in the Elevation of Adenosine Cyclic 3',5'-Monophosphate and Induction of Serotonin <em>N</em>-Acetyltransferase in Rat Pineal Glands
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 184
OP 190
VO 9
IS 2
A1 TAKEO DEGUCHI
YR 1973
UL http://molpharm.aspetjournals.org/content/9/2/184.abstract
AB 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. ACKNOWLEDGMENT The author thanks Dr. Julius Axelrod for his helpful suggestions and encouragement throughout this study.