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[The Involvement of Phosphoinositide 3-kinase (PI3-Kinase) and Phospholipase C Gamma (PLC Gamma) Pathway in the Morphine-Induced Supraspinal Antinociception in the Mouse]

[The Involvement of Phosphoinositide 3-kinase (PI3-Kinase) and Phospholipase C Gamma (PLC Gamma) Pathway in the Morphine-Induced Supraspinal Antinociception in the Mouse]

M Narita, O Ohnishi, M Nemoto, T Aoki, T Suzuki

Nihon Shinkei Seishin Yakurigaku Zasshi. 2001 Feb;21(1):7-14.

PMID: 11400324

Abstract:

The present study was designed to investigate whether the phospholipase C gamma (PLC gamma)/phosphoinositide 3-kinase (PI3-Kinase) pathway could participate in the expression of the supraspinal antinociception induced by intracerebroventricular (i.c.v.) administration of mu-opioid receptor agonist in the mouse. The i.c.v. pretreatment with PI3-Kinase inhibitors, wortmannin and LY294002, and a specific antibody to PLC gamma 1 significantly attenuated the antinociception produced by either i.c.v. or systemic (s.c.) injection of a prototype of mu-agonist morphine. The s.c. injection of morphine produced a marked increase in the level of membrane-bound PLC gamma 1 isoform as compared to that from the saline-treated mice. This up-regulation of PLC gamma 1 by morphine was significantly inhibited by i.c.v. pretreatment with LY294002, indicating that morphine can activate PLC gamma 1 through the stimulation of PI3-Kinase. Pretreatment with a specific IP3 receptor inhibitor xestospongin C suppressed the morphine-induced antinociception in a dose-dependent manner. Recent studies have demonstrated that PI3-Kinase can be activated by G beta gamma, but not by G alpha subunit. In the present study, i.c.v. pretreatment with specific antibodies to G12 alpha and G beta gamma significantly suppressed the antinociception induced by morphine, whereas the specific antibody to Gq/11 alpha did not affect the antinociception induced by morphine. The present findings suggest that the supraspinal antinociception induced by mu-opioid receptor agonist may be mediated, at least in part, by the activation of PLC gamma through the stimulation of PI3-Kinase modulated by G beta gamma subunit.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417893	MonoclonalAnti-PP2A, C subunit antibody produced in mouse			Price

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