Interaction of the alpha-2 adrenergic- and opioid receptor with the cGMP system in the mouse cerebellum

The alpha-2 adrenergic agonist dexmedetomidine (Dex), 3-300 mu g/kg, i.p., decreased cerebellar cGMP in a dose-dependent manner. Fentanyl (F), an opio id agonist, increased cerebellar cGMP at 0.3 mg/kg, s.c., and decreased it at doses greater than or equal to 1 mg/kg. The inhibitory effect was recept or specific, that of Dex being blocked by the a-2 adrenergic antagonist yoh imbine, 5 mg/kg, i.p.; that of F by the opioid antagonist naloxone, 5 mg/kg , i.p. In contrast the stimulatory effect of F was blocked by both naloxone and yohimbine. Yohimbine also enhanced the inhibitory effect of F. In mice pretreated with pertussis toxin, 2 mu g/mouse, given i.c.v. 72 h before th e agonists, the decrease in cGMP induced by Dex or F was not affected, whil e the stimulatory effect of F was reversed to an inhibitory effect. When in hibiting doses of F and Dex were administered together, the cGMP response w as smaller than the sum of the individual responses. Dex attenuated in a do se-dependent manner the decrease in cGMP induced by F, and unmasked or enha nced the stimulatory effect of F. These results show that the alpha-2 adren ergic- and opioid-receptors are coupled to the cGMP effector system and sug gest that the two pathways converge at a common post-receptor site in the c ascade of events transducing the receptor signal to cGMP regulation. (C) 19 98 Published by Elsevier Science B.V. All rights reserved.