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 microg/kg, i.p., decreased cerebellar cGMP in a dose-dependent manner. Fentanyl (F), an opioid agonist, increased cerebellar cGMP at 0.3 mg/kg, s.c., and decreased it at doses >/=1 mg/kg. The inhibitory effect was receptor specific, that of Dex being blocked by the alpha-2 adrenergic antagonist yohimbine, 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 microgram/mouse, given i.c.v. 72 h before the agonists, the decrease in cGMP induced by Dex or F was not affected, while the stimulatory effect of F was reversed to an inhibitory effect. When inhibiting doses of F and Dex were administered together, the cGMP response was smaller than the sum of the individual responses. Dex attenuated in a dose-dependent manner the decrease in cGMP induced by F, and unmasked or enhanced the stimulatory effect of F. These results show that the alpha-2 adrenergic- and opioid-receptors are coupled to the cGMP effector system and suggest that the two pathways converge at a common post-receptor site in the cascade of events transducing the receptor signal to cGMP regulation.
Vulliemoz
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Y
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. yv4@columbia.edu
Virag
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L
Whittington
R A
RA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D005283:Fentanyl / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D007093:Imidazoles; D009292:Narcotic Antagonists; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D015016:Yohimbine; D009270:Naloxone; D006152:Cyclic GMP; D020926:Medetomidine; D005283:Fentanyl