Mu type opioid receptors in rat periaqueductal gray-enriched P2 membrane are coupled to G-protein-mediated inhibition of adenylyl cyclase.
The periaqueductal gray (PAG) region of the midbrain has been implicated in both stimulation-produced and opioid-induced analgesia. High-affinity mu-selective opioid-binding sites associated with mu type opioid receptors have been detected in rat PAG-enriched P2 membranes, and these receptors have been shown to be coupled to guanine nucleotide-binding proteins (G-proteins). In the present study the potential G-protein-mediated coupling of mu type opioid receptors to the inhibition of adenylyl cyclase was examined utilizing in vitro adenylyl cyclase assays. In the presence of Na+, opioid agonists inhibited adenylyl cyclase in a mu selective, naloxone reversible, dose dependent, and pertussis toxin sensitive manner. Overall the data suggests that mu type opioid receptors in the rat PAG are coupled to G-protein-mediated inhibition of adenylyl cyclase.
Fedynyshyn
J P
JP
Department of Pharmacology, University of California, San Francisco 94143-0450.
Lee
N M
NM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D010487:Periaqueductal Gray / Q000502:physiology*; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins