title: Modulation of rat brain opioid receptors by cannabinoids.
abstract: The interaction of delta 9-tetrahydrocannabinol (delta 9-THC) and related cannabinoids with opioid receptors of neuronal membranes has been investigated. Treatment of membranes with delta 9-THC consistently decreased specific in vitro binding of [3H]dihydromorphine (mu opioid) in a dose-dependent fashion. Similar dose-dependent changes were elicited by cannabidiol and (+/-)-hexahydrocannabinol. Equilibrium binding studies in which brain membranes were titrated with [3H]dihydromorphine in the presence of delta 9-THC demonstrated that the decrease in [3H]dihydromorphine binding is due to a reduction in the number of binding sites, with no significant alteration in receptor affinity. This result suggests that the interaction of delta 9-THC with opioid receptors is a noncompetitive one. Delta 9-THC also inhibited the binding of the delta opioid [3H]D-Pen2, D-Pen5-enkephalin and the opioid antagonist [3H]naloxone (Ki = 16 and 19 microM, respectively) but failed to inhibit the binding of the kappa opioid [3H]ethylketocyclazocine (after suppression of mu and delta receptor binding), the phencyclidine analog [3H]N-(1-[2-theinyl]cyclohexyl)piperidine, the dopamine antagonist [3H]spiroperidol or the muscarinic antagonist [3H]quinuclidinyl benzilate. Moreover, delta 9-THC inhibited the binding of [3H]etorphine (potent opioid agonist) to solubilized, partially purified opioid receptors with a Ki value similar to that observed for the membrane-bound receptors. This finding indicates that the allosteric modulation of the opioid receptor by delta 9-THC is the result of a direct interaction with the receptor protein or with a specific protein-lipid complex and not merely the result of a perturbation of the lipid bilayer of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine; D005048:Etorphine / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D005048:Etorphine; D013134:Spiperone; D016314:Ethylketocyclazocine; D013759:Dronabinol; D020881:Enkephalin, D-Penicillamine (2,5)-; D004090:Dihydromorphine; D003496:Cyclazocine