Pharmacologic characterization of melatonin-mediated phosphoinositide hydrolysis in pigeon brain.
High densities of [125I]-iodomelatonin binding sites have been demonstrated in pigeon brain. Melatonin binding sites have been shown to be linked to signal transduction mechanisms in other species. The present study investigated the melatonin-mediated second messenger response of phosphoinositide hydrolysis in slices of telencephalon, optic tectum, cerebellum, hypothalamus, and pons medulla of pigeon brain. The highest rates of melatonin-mediated phosphoinositide hydrolysis were observed in telencephalon and pons/medulla. Relative potencies of melatonin agonists to induce phosphoinositide hydrolysis were as follows: 2-iodomelatonin > 6-chloromelatonin > N-acetylserotonin > melatonin > > serotonin (5-HT). Agonist-induced phosphoinositide hydrolysis was blocked by N-acetyltryptamine (NAT), a melatonin antagonist, but not by ketanserin, a 5HT2A/2C receptor antagonist, demonstrating that phosphoinositide hydrolysis did not result from 5HT2A or 5HT2C receptor stimulation. In addition, the effects of melatonin agonists were sensitive to prazosin, an alpha-adrenergic antagonist reported to exhibit nanomolar affinity for melatonin binding sites in hamster brain, but not to phentolamine, an alpha-adrenergic antagonist that shows no affinity for melatonin binding sites. These data provide evidence that signal transduction associated with melatonin in pigeon brain involves the induction of phosphoinositide hydrolysis as a second messenger.
CNS Special Projects, Bristol-Myers Squibb Company, Wallingford, CT 06492-7660.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D010856:Columbidae; D006868:Hydrolysis; D007650:Ketanserin / Q000494:pharmacology; D008550:Melatonin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology; D014363:Tryptamines / Q000494:pharmacology
D010716:Phosphatidylinositols; D014363:Tryptamines; C043464:N-acetyltryptamine; D007650:Ketanserin; D008550:Melatonin