Differential modulation of GABAA receptor function by Mel1a and Mel1b receptors

Melatonin, a hormone principally produced and released by the pineal gland, has been shown to regulate a variety of biological functions including circadian rhythms, sleep-wake cycles and reproduction1, presumably through activating high-affinity G-protein-coupled receptors2,3,4,5. We report here that these subtypes can differentially modulate the function of type-A γ-aminobutyric acid (GABAA) receptor, the principal neurotransmitter receptor mediating synaptic inhibition in the CNS6,7. This work demonstrates that melatonin, through activation of different receptor subtypes, can exert opposite effects on the same substrate, suggesting that receptor subtype is the primary molecular basis for the diversity of melatonin effects.