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Titolo:
Protein kinase C-mediated inhibition of mu-opioid receptor internalizationand its involvement in the development of acute tolerance to peripheral mu-agonist analgesia
Autore:
Ueda, H; Inoue, M; Matsumoto, T;
Indirizzi:
Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, Nagasaki8528521, Japan Nagasaki Univ Nagasaki Japan 8528521 & Neurosci, Nagasaki8528521, Japan
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 9, volume: 21, anno: 2001,
pagine: 2967 - 2973
SICI:
0270-6474(20010501)21:9<2967:PKCIOM>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOWN-REGULATION; IN-VIVO; HOMOLOGOUS DESENSITIZATION; DIFFERENTIAL REGULATION; NOCICEPTIVE RESPONSES; MOLECULAR MECHANISMS; SIGNAL-TRANSDUCTION; XENOPUS OOCYTES; SUBSTANCE-P; DELTA;
Keywords:
protein kinase C; peripheral acute tolerance; internalization; mu-opioid receptor; dynamin; K44A/dynamin adenovirus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Ueda, H Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, 1-14 Bunkyo Machi, Nagasaki 8528521, Japan Nagasaki Univ 1-14 Bunkyo Machi Nagasaki Japan 8528521 521, Japan
Citazione:
H. Ueda et al., "Protein kinase C-mediated inhibition of mu-opioid receptor internalizationand its involvement in the development of acute tolerance to peripheral mu-agonist analgesia", J NEUROSC, 21(9), 2001, pp. 2967-2973

Abstract

We investigated the role of protein kinase C (PKC) in cell mu -opioid receptor (MOR) internalization and MOR-mediated acute tolerance in vivo. When Chinese hamster ovary cells expressing MOR were exposed to [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (DAMGO), receptor internalization was observed at 30min. Incubation with morphine failed to induce receptor internalization. When calphostin C, a PKC inhibitor, was added, receptor internalization was observed as early as 10 min after morphine stimulation. The MOR internalization induced by DAMGO or morphine in the presence of calphostin C was dynamin dependent, because it was abolished 2 d after pretreatment with recombinant adenovirus to express a dominant interfering dynamin mutant (K44A/dynamin adenovirus). On the other hand, in a peripheral nociception test in mice, the nociceptive flexor response after intraplantar injection (i.pl.) of bradykinin was markedly inhibited by DAMGO (i.pl.). DAMGO analgesia was not affected by 2 hr prior injection (i.pl.) of DAMGO. Marked acute tolerance was observed after pretreatment with dynamin antisense oligodeoxynucleotide or K44A/dynamin adenovirus. The DAMGO-induced acute tolerance under such pretreatments was inhibited by calphostin C. Together, these findings suggestthat PKC desensitizes MOR or has a role in the development of acute tolerance through MOR by inhibiting internalization mechanisms as a resensitization process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 05:22:42