STIMULATION OF CAMP ACCUMULATION BY THE CLONED XENOPUS MELATONIN RECEPTOR THROUGH G(I) AND G(Z) PROTEINS

The Xenopus melatonin receptor mas expressed in human embryonic kidney 293 cells and assayed for cAMP accumulation, In transfected 293 cells expressing the melatonin receptor, melatonin dose-dependently inhibited the endogenous adenylyl cyclases, In contrast, melatonin stimulated the accumulation of cAMP in cells co-expressing the type II adenylyl cyclase, Both the inhibitory and stimulatory responses to melatonin mere mediated via G(i)-like proteins as they mere blocked by pertussis toxin, Upon co-transfection with the alpha subunit of G(z), the ability of melatonin to regulate both type II and the endogenous adenylyl cyclases became refractory to pertussis toxin, indicating that the melatonin receptor can also couple to G(z), However, other pertussis toxin-insensitive G proteins such as G(q), G(12) and G(13) were unable to interact with the melatonin receptor.