Agonistic action of 2-phenylmelatonin on adenylyl cyclase activity in the rat hypothalamus

The melatonin analog, 2-phenylmelatonin, has been reported to act as either an agonist or antagonist in various biological systems. In order to further clarify the pharmacological properties of this compound, its effects on melatonin signalling in the rat hypothalamus were examined. As expected, melatonin (10^-11-10^-8 M) inhibited forskolin-stimulated adenylyl cyclase (AC) activity by about 25-30% in hypothalamic membranes. Similar concentrations of 2-Phenylmelatonin also inhibited stimulated AC activity by about 20%. Moreover, when the indoles were added together in enzyme assays, 2-phenylmelatonin did not antagonize the suppressive effect of melatonin on AC activity. These findings indicate that 2-phenylmelatonin is a melatonergic agonist in the rat hypothalamic AC model.