| 12782184 |
Wang SJ: Cannabinoid CB1 receptor-mediated inhibition of glutamate release from rat hippocampal synaptosomes. Eur J Pharmacol. 2003 May 23;469(1-3):47-55.
Cannabinoid receptors are widely expressed in the brain and have been shown to regulate synaptic transmission through a presynaptic mechanism. Using synaptosomal preparation, I show here that 2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)-pyrrolo-1,4-benzoxazin-6-yl- 1-naphthalenylmethanone (WIN 55212-2) strongly depressed 4-aminopyridine-evoked glutamate release in a concentration-dependent manner, and this effect was reversed by the selective cannabinoid CB (1) receptor antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazo le-3-carboxamide (AM 281). The inhibitory modulation by WIN 55212-2 was not due to a decrease in synaptosomal excitability or a direct effect on the release machinery because WIN 55212-2 did not alter 4-aminopyridine-mediated depolarization and ionomycin-induced glutamate release. In addition, the WIN 55212-2-mediated inhibition of glutamate release was blocked by the G (i)/G (o) protein inhibitor pertussis toxin, but not by the protein kinase A inhibitor 2,3,9,10,11,12-Hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo- benzodiazocine-10-carboxylic acid, hexyl ester (KT 5720). Furthermore, this inhibitory effect was associated with a decrease in 4-aminopyridine-evoked Ca (2+) influx, which could be completely prevented in synaptosomes pretreated with the N- and P/Q-type Ca (2+) channel blockers. Together, these observations indicate that activation of cannabinoid CB (1) receptors inhibit 4-aminopyridie-evoked glutamate release from hippocampal synaptosomes through a inhibitory G protein to suppress N- and P/Q-type Ca (2+) channel activity. |
0(0,0,0,0) |