Pertussis toxin blocks melatonin-induced inhibition of forskolin-stimulated adenylate cyclase activity in the chick brain

The high-affinity guanine nucleotide-sensitive receptor sites for melatonin in the mammalian hypothalamus and pars tuberalis mediate inhibition of adenylate cyclase (AC) activity. Therefore, we have examined whether similar sites in the chick brain and retina also modulate AC activity. Melatonin did not alter basal or forskolin-stimulated AC activity in whole forebrain or retinal homogenates. In contrast, melatonin significantly inhibited forskolin-stimulated AC activity in forebrain synaptosomal membranes and partially purified retinal membranes in a concentration-dependent manner. Maximal inhibition (approximately 25-30%) of stimulated AC activity was observed at 10-100nM melatonin, while the concentrations (EC50's) which caused half-maximal effects were 22 +/- 6 pM and 30 +/- 5 pM in the brain and retina respectively. Pretreatment of forebrain slices with pertussis toxin abolished the inhibitory effect of melatonin on stimulated AC activity. These data provide the first evidence that melatonin suppresses AC activity in the chick CNS via a pertussis toxin-sensitive G-protein.