title: Opioid desensitization: interactions with G-protein-coupled receptors in the locus coeruleus.
abstract: In rat locus coeruleus (LC) neurons, alpha 2 adrenoceptors, mu-opioid and somatostatin receptors all activate the same potassium conductance. Chronic treatment with morphine causes a loss of sensitivity that is specific to the mu-opioid response, with no change in the alpha 2 adrenoceptor-mediated response. Acute desensitization induced by opioid, somatostatin, and alpha 2-adrenoceptor agonists was studied in brain slices of rat LC using intracellular recording. A supramaximal concentration of the opioid agonist Met5-enkephalin induced a profound homologous desensitization but little heterologous desensitization to an alpha 2-adrenoceptor agonist (UK 14304) or somatostatin. All desensitized currents showed partial recovery. A supramaximal concentration of UK14304 caused a relatively small amount of desensitization. Although little interaction was observed among inhibitory G-protein-coupled receptors, activation of an excitatory receptor had marked effects on inhibitory responses. Muscarinic agonists, which produce an inward current in LC neurons, reduced the magnitude of agonist-induced outward currents and increased both the rate and amount of opioid desensitization. Muscarinic activation did not alter desensitization of alpha 2-adrenoceptor responses. Acute desensitization shares several characteristics with the tolerance induced by chronic morphine treatment of animals.
authors.affiliation: Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Fiorillo
authors.forename: J T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004361:Drug Tolerance; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D004745:Enkephalins; D011810:Quinoxalines; D017450:Receptors, Opioid, mu; D000068438:Brimonidine Tartrate; D009116:Muscarine; D019204:GTP-Binding Proteins