Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and zeta isoforms in the frontal cortex of human opiate addicts.
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.
García-Sevilla
J A
JA
Department of Psychiatry, Faculty of Medicine, University of Geneva, Switzerland.
Ventayol
P
P
Busquets
X
X
La Harpe
R
R
Walzer
C
C
Guimón
J
J
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*
D017450:Receptors, Opioid, mu; D011493:Protein Kinase C