8971779

pubmed:Citation

1

The effects of pretreatment with a protein kinase C activator, phorbol 12,13-dibutyrate, on antinociception induced by i.c.v.-administered mu-opioid receptor agonist (D-Ala2, NMePhe4, Gly(ol)5) enkephalin (DAMGO) or morphine and epsilon-opioid receptor agonist beta-endorphin were studied in male ICR mice. The tail-flick responses were used for antinociceptive tests. I.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol) for 30 or 60 but not 10 min attenuated antinociception induced by i.c.v.-administered DAMGO. I.c.v. pretreatment with phorbol 12,13-dibutyrate (10 and 50 pmol) for 60 min caused a dose-dependent attenuation of DAMGO (19.5 pmol)- or morphine (6.0 nmol)-induced antinociception. The dose-response curve for DAMGO-induced antinociception was shifted to the right by 7.3-fold by i.c.v. pretreatment with phorbol 12,13-dibutyrate (50 pmol) for 60 min. However, the i.c.v.-administered beta-endorphin-induced antinociception was not affected by the same pretreatment with phorbol 12,13-dibutyrate. The attenuation of i.c.v.-administered DAMGO- and morphine-induced antinociception by phorbol 12,13-dibutyrate was reversed by concomitant i.c.v. pretreatment with a selective protein kinase C inhibitor calphostin C. These results suggest that activation of protein kinase C by phorbol 12,13-dibutyrate leads to the desensitization of mu-, but not epsilon-opioid receptor-mediated antinociception. These findings also provide additional evidence for differential intracellular modulation on antinociceptive action of mu- and epsilon-opioid receptor agonists.

eng

IM

MEDLINE

0306-4522

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NLM

291-8

pubmed-meshheading:8971779-Analgesics, pubmed-meshheading:8971779-Animals, pubmed-meshheading:8971779-Dose-Response Relationship, Drug, pubmed-meshheading:8971779-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:8971779-Enkephalins, pubmed-meshheading:8971779-Enzyme Activation, pubmed-meshheading:8971779-Enzyme Inhibitors, pubmed-meshheading:8971779-Injections, Intraventricular, pubmed-meshheading:8971779-Male, pubmed-meshheading:8971779-Mice, pubmed-meshheading:8971779-Mice, Inbred ICR, pubmed-meshheading:8971779-Naphthalenes, pubmed-meshheading:8971779-Nociceptors, pubmed-meshheading:8971779-Pain Measurement, pubmed-meshheading:8971779-Phorbol 12,13-Dibutyrate, pubmed-meshheading:8971779-Protein Kinase C, pubmed-meshheading:8971779-Receptors, Opioid, pubmed-meshheading:8971779-Receptors, Opioid, mu, pubmed-meshheading:8971779-Time Factors, pubmed-meshheading:8971779-beta-Endorphin

Pretreatment with protein kinase C activator phorbol 12,13-dibutyrate attenuates the antinociception induced by mu- but not epsilon-opioid receptor agonist in the mouse.

Journal Article, Research Support, U.S. Gov't, P.H.S.