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Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase
Author(s) -
Maneuf Yannick P,
McKnight Alexander T
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704227
Subject(s) - adenylyl cyclase , forskolin , protein kinase c , adcy10 , glutamate receptor , chelerythrine , chemistry , adcy9 , stimulation , protein kinase a , endocrinology , medicine , activator (genetics) , biology , biochemistry , signal transduction , kinase , receptor
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 n M ), but in the presence of gabapentin (30 μ M ) 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 μ M ), and again this facilitatory effect was blocked by gabapentin (30 μ M ). 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. British Journal of Pharmacology (2001) 134 , 237–240; doi: 10.1038/sj.bjp.0704227