title: Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and zeta isoforms in the frontal cortex of human opiate addicts.
abstract: To assess the status of opioid receptors in the human brain during the process of opiate addiction, the abundance of immunoreactive mu-opioid receptors was quantitated in postmortem brains of chronic opiate addicts who had died of a heroin or methadone overdose. The immunoreactive levels of the associated enzyme protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2) subunits) were also assessed in the same brains. In the frontal cortex of opiate addicts, the abundance of mu-opioid receptors was not different from that obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G alpha(i1/2) proteins also was found to be increased (40%). The results indicate that opiate addiction in humans does not appear to be associated with a reduced density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2) proteins aimed at compensating the postulated desensitization of the mu-opioid receptor system.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sevilla
authors.forename: P
authors.initials: P
authors.lastname: Ventayol
authors.forename: X
authors.initials: X
authors.lastname: Busquets
authors.forename: R
authors.initials: R
authors.lastname: La Harpe
authors.forename: C
authors.initials: C
authors.lastname: Walzer
authors.forename: J
authors.initials: J
authors.lastname: Guimón
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005625:Frontal Lobe / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D017450:Receptors, Opioid, mu; D011493:Protein Kinase C