Parallel modulation of receptor for activated C kinase 1 and protein kinase C‐α and β isoforms in brains of morphine‐treated rats

• Published in: British journal of pharmacology 1999-05, Vol.127 (2), p.343-348
• Main Authors: Escriba, P V, Garcia-Sevilla, JA
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - enzymology; cytoskeleton; Drug addictions; Immunoblotting; Isoenzymes - metabolism; Male; Medical sciences; Morphine; Morphine - pharmacology; Naloxone - pharmacology; Narcotics - pharmacology; opiate addiction; opioid receptors; Peptides - metabolism; Prefrontal Cortex - drug effects; Prefrontal Cortex - enzymology; Protein Kinase C - metabolism; Protein Kinase C beta; Protein Kinase C-alpha; protein kinase C; rat brain; Rats; Rats, Sprague-Dawley; receptor for activated C kinase 1; Receptors for Activated C Kinase; Toxicology; Tubulin - metabolism; Up-Regulation - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702555

Receptor for activated C kinase 1 (RACK1) is an intracellular receptor for protein kinase C (PKC) that regulates the cellular enzyme localization. Because opiate drugs modulate the levels of brain PKC (Ventayol et al., 1997), the aim of this study was to assess in parallel the effects of morphine on RACK1 and PKC‐α and β isozymes densities in rat brain frontal cortex by immunoblot assays. Acute morphine (30 mg kg−1, i.p., 2 h) induced significant increases in the densities of RACK1 (33%), PKC‐α (35%) and PKC‐β (23%). In contrast, chronic morphine (10–100 mg kg−1, i.p., 5 days) induced a decrease in RACK1 levels (22%), paralleled by decreases in the levels of PKC‐α (16%) and PKC‐β (16%). Spontaneous (48 h) and naloxone (2 mg kg−1, i.p., 2 h)‐precipitated morphine withdrawal after chronic morphine induced marked up‐regulations in the levels of RACK1 (38–41%), PKC‐α (51–52%) and PKC‐β (48–62%). In the same brains and for all combined treatments, there were significant positive correlations between the density of RACK1 and those of PKC‐α (r=0.85, n=35) and PKC‐β (r=0.75, n=32). These data indicate that RACK1 is involved in the short‐ and long‐term effects of morphine and in opiate withdrawal, and that RACK1 modulation by morphine or its withdrawal is parallel to those of PKC‐α and β isozymes. Since RACK1 facilitates the PKC substrate accessibility, driving its cellular localization, the coordinate regulation of the PKC/RACK system by morphine could be a relevant molecular mechanism in opiate addiction. British Journal of Pharmacology (1999) 127, 343–348; doi:10.1038/sj.bjp.0702555