Presynaptic effects of melatonin on norepinephrine release and uptake in rat pineal gland

Abstract: The effect of melatonin injection on norepinephrine (NE) turnover rate in rat pineal gland was estimated from the decline of tissue NE levels after the injection of the tyrosine hydroxylase inhibitor α‐methyl‐p‐tyrosine. The administration of a single injection of 300 μg/Kg of melatonin at the beginning of the scotophase induced, 3 hr later, a significant decrease of pineal NE turnover. The possible direct effect of melatonin on pineal NE release was examined in vitro. Exposure of rat pineal expiants previously loaded with ³H‐NE to 10⁻⁸‐10⁻⁶ M melatonin decreased significantly ³H‐NE release triggered by 60 mM K⁺. This activity of melatonin was revealed only in pineals excised at night (0000 and 0400, i.e., at the fourth or eighth hours of darkness) and not in those excised in the middle (1400) or late light phase of the daily photoperiod (2000). Melatonin did not modify the spontaneous pineal ³H‐NE efflux. Melatonin decreased ³H‐NE uptake at a low NE concentration (0.5 μM) in a dose‐dependent manner (IC₅₀≡ 10⁻¹⁰ M). A kinetic analysis of the pineal NE uptake process indicated that melatonin augmented both V_max and K_m of transmitter uptake. These results suggest that endogenously released melatonin may be a regultory signal for rat pineal sympathetic synapses.