In vivo observation of a non-noradrenergic regulation of arylalkylamine N-acetyltransferase gene expression in the rat pineal complex

The rodent pineal gland is the end point of several peripheral and central fibers innervating the superficial and deep parts of the gland. Up to now, only the sympathetic transmitter norepinephrine is thought to regulate mela tonin synthesis, although numerous biochemical experiments have reported in vitro effects of various transmitters on melatonin synthesis. To find out whether there is non-noradrenergic regulation of in vivo pineal metabolism, the mRNA encoding the enzyme arylalkylamine N-acetyltransferase was studie d using the highly sensitive technique of in situ hybridization. The existe nce of a marked nocturnal increase of arylalkylamine N-acetyltransferase mR NA in the superficial pineal gland was confirmed. Interestingly and for the first time, a similar daily variation was observed in the deep pineal. Aft er removal of superior cervical ganglia, the daily rhythm in arylalkylamine N-acetyltransferase mRNA was abolished in both the superficial and deep pi neal indicating that the rhythm is driven by sympathetic input in the entir e pineal complex. Interestingly, the remaining arylalkylamine N-acetyltrans ferase mRNA level in the pineal of day- and nighttime ganglionectomized rat s was significantly higher than in the pineal of day-time intact animals. T hese data reveal a sympathetic-dependent day-time inhibition of arylalkylam ine N-acetyltransferase gene expression. In addition, the daytime pineal ar ylalkylamine N-acetyltransferase mRNA expression in ganglionectomized rats persisted after adrenal gland removal but was reduced by 50% after proprano lol injection. These results indicate that arylalkylamine N-acetyltransfera se mRNA in ganglionectomized rats is not induced by circulating catecholami nes and may be caused by both a centrally originated norepinephrine, as alr eady suggested, and other non-adrenergic transmitter(s). In conclusion, this work shows that norepinephrine drives the nocturnal inc rease of arylalkylamine N-acetyltransferase gene expression both in the sup erficial and deep pineal and strongly suggests that other neurotransmitters are involved in day-time inhibition and night-time stimulation of pineal m etabolism. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights res erved.