Ethanol reduces norepinephrine-stimulated melatonin synthesis in rat pinealocytes

In this study, the in vitro effects of ethanol on norepinephrine-stimulated cyclic AMP (cAMP), N-acetyltransferase (NAT), and melatonin (MT) production were examined in dispersed rat pinealocytes. Cellular cAMP content was determined 15 min after treatment; whereas NAT activity and MT release in the medium were determined 4.5 h after treatment. It was found that ethanol less than or equal to 200 mM had no effect on norepinephrine-stimulated cAMP response, whereas 25 mM ethanol resulted in a significant inhibition of norepinephrine-stimulated NAT and MT levels. Furthermore, ethanol was equally effective in inhibiting the dibutyryl cAMP-stimulated NAT and MT levels. The inhibitory action of ethanol was not due to a direct effect or a delay in the onset of NAT activity. When alcohols with different chain lengths were used, it was found that their inhibitory potencies were related to their chain lengths with butanol greater than propanol greater than ethanol greater than methanol. Taken together, these findings indicate that (1) ethanol has an inhibitory action on norepinephrine-stimulated MT synthesis, (2) one site of ethanol action is distal to cAMP elevation, and (3) the inhibitory effect of ethanol on pineal MT synthesis appears to be secondary to its hydrophobic action.