当前位置： SCI文献检索 > BRITISH JOURNAL OF ANAESTHESIA期刊下所有文献 > Effect of halothane on conventional protein kinase C translocation and down-regulation in rat cerebrocortical synaptosomes.

Effect of halothane on conventional protein kinase C translocation and down-regulation in rat cerebrocortical synaptosomes.

Abstract：

:Protein kinase C (PKC) is a key regulatory enzyme that has been implicated as a molecular target for the action of general anaesthetics. We have determined the effects of halothane on the translocation and down-regulation of conventional PKC (cPKC) by analysing the subcellular distribution of PKC activity, [3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding and PKC immunoreactivity in intact rat cerebrocortical synaptosomes, a subcellular fraction that contains functional nerve terminals. Halothane alone (2.4 vol%) reduced membrane-associated (P < 0.05) and increased cytosol (P < 0.01) PKC activity, while phorbol-12-myristate, 13-acetate (PMA) 0.1 mumol litre-1, a metabolically stable activator of PKC, reduced membrane (P < 0.01) without altering cytosol PKC activity. Halothane and PMA in combination reduced membrane PKC activity to undetectable levels and reduced cytosol PKC activity (P < 0.01). Halothane alone had no significant effects on the distribution of [3H]PDBu binding, while PMA alone significantly reduced both membrane and cytosol [3H]PDBu binding (P < 0.01). Halothane and PMA in combination reduced membrane and cytosol [3H]PDBu binding further, but this effect was not significantly different from the effect of PMA alone. Experiments using isoform-selective antibodies to PKC alpha, PKC beta or PKC gamma demonstrated synergistic interactions between halothane and PMA in promoting translocation of the three conventional PKC isoforms from the cytosol to the membrane fraction of synaptosomes and down-regulation of their immunoreactivity. Halothane and PMA together reduced cytosol PKC alpha/beta/gamma immunoreactivity significantly more (P < 0.05) than PMA alone. Halothane thus has two distinct actions on PKC in synaptosomes: activation of endogenous PKC activity and potentiation of activation-induced cPKC translocation and down-regulation. These potentially competing effects may underlie some of the conflicting results obtained with halothane on PKC-mediated processes in intact cells.

journal_name

Br J Anaesth

journal_title

British journal of anaesthesia

authors

Hemmings HC Jr,Adamo AI

doi

10.1093/bja/78.2.189

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

189-96

issue

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)41983-0

journal_volume

pub_type

杂志文章

在线工具

Effect of halothane on conventional protein kinase C translocation and down-regulation in rat cerebrocortical synaptosomes.