Abstract

Norepinephrine or isoproterenol injected into rats increases serotonin N-acetyltransferase (EC 2.3.1.5) activity many fold in the pineal gland. One or two days after denervation by bilateral ganglionectomy, norepinephrine produced a 5-10-fold higher increase in N-acetyltransferase activity than in intact pineals. When low doses of isoproterenol are injected, N-acetyltransferase activity in denervated pineals increases much more than in intact pineals, while high doses result in similar increases in N-acetyltransferase activity in intact and denervated pineals. Intact pineals cultured in the presence of norepinephrine show maximal increases in N-acetyltransferase activity at about 10 µM, whereas maximal increases are observed in denervated pineals at 20 nM norepinephrine. Isoproterenol (0.1-1 µM) causes a maximal increase in enzyme activity in intact pineals, whereas 4 nM isoproterenol increases N-acetyltransferase activity to the maximal level in denervated pineals. The concentration of catecholamines in culture required for the maximal increase in N-acetyltransferase activity differs by almost 100-fold for norepinephrine and by 20-fold for isoproterenol between intact did denervated pineals. Maximal enzyme activity, however, is the same in both intact and denervated pineals. The elevation of adenosine cyclic 3',5'-monophosphate levels in denervated pineals greatly exceeds that in intact pineals when submaximal doses of either norepinephrine or isoproterenol are injected into rats. When pineals are cultured in the presence of dibutyryladenosine cyclic 3',5'-monophosphate, there is no difference in the increase of N-acetyltransferase activity between intact and denervated pineals. These results indicate that denervation induces rapid supersensitivity in the postsynaptic beta adrenergic receptor site on the pineal cell to catecholamines, which in turn enhances the elevation of adenosine cyclic 3',5'-monophosphate and results in the superinduction of N-acetyltransferase in the pineal gland.