Up-regulation of mu-opioid receptor-mediated G-protein activation in protein kinase Cgamma knockout mice following repeated naloxone treatment.
The aim of the present study was to investigate whether repeated treatment with the mu-opioid receptor antagonist naloxone could affect G-protein activation induced by a selective mu-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) in mice lacking the protein kinase Cgamma isoform monitoring guanosine-5'-o-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding. Repeated s.c. administration of naloxone for 7 days resulted in a significant enhancement of the increased [(35)S]GTPgammaS binding by DAMGO to membranes of the spinal cord obtained from mice lacking the protein kinase Cgamma isoform. Furthermore, immunoreactivities of membrane-located protein kinase Cgamma and phosphorylated-protein kinase C in the spinal cord of ICR mice were not altered by repeated naloxone treatment. The present data provide direct evidence that protein kinase Cgamma is not involved in the development of the up-regulation of mu-opioid receptor functions to activate G-proteins in the mouse spinal cord by repeated naloxone treatment.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan.
Suzuki
Masami
M
Mizoguchi
Hirokazu
H
Narita
Michiko
M
Yajima
Yoshinori
Y
Sakurada
Shinobu
S
Tseng
Leon F
LF
Suzuki
Tsutomu
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology; D015854:Up-Regulation
D007527:Isoenzymes; D009292:Narcotic Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C087857:protein kinase C gamma; D011493:Protein Kinase C; D019204:GTP-Binding Proteins