Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase.

Abstract:

:The effect of activation of protein kinase C (PKC) or adenylyl cyclase on release of glutamate has been investigated in a perfused slice preparation from the rat caudal trigeminal nucleus. Stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) produced a concentration-dependent increase in K(+)-evoked release of [(2)H]-glutamate (maximum increase 45%, EC(50) 11.8 nM), but in the presence of gabapentin (30 microM) the facilitation of release was blocked. The adenylyl cyclase activator forskolin (FSK) also induced a concentration-dependent increase in K(+)-evoked release of [(3)H]-glutamate (maximum increase 36%, EC(50) 2.4 microM), and again this facilitatory effect was blocked by gabapentin (30 microM). We suggest that these results may be of relevance to the antihyperalgesic properties of gabapentin, in conditions where concomitant release of substance P and CGRP produces activation of PKC and adenylyl cyclase respectively.

journal_name

Br J Pharmacol

authors

Maneuf YP,McKnight AT

doi

10.1038/sj.bjp.0704227

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

237-40

issue

2

eissn

0007-1188

issn

1476-5381

journal_volume

134

pub_type

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