title: Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens.
abstract: We investigated the role of endogenous protein kinase activity on synaptic transmission in the rat nucleus accumbens slice. The isoquinolinesulfonamide H-7 (50muM), a non-selective serine/threonine protein kinase inhibitor, had no effect on pharmacologically isolated glutamatergic EPSCs. However, it reduced GABA release in a dose-dependent manner. This effect of H-7 was not mimicked by the selective cAMP-dependent protein kinase inhibitor H-89, the PKC inhibitor Bisindolylmaleimide-1, or the cGMP-dependent protein kinase inhibitor KT5823. However, bath application of the myosin light chain kinase (MLCK) inhibitor, ML-7, significantly reduced IPSC amplitudes and partially occluded the reduction in IPSCs observed following bath application of H-7. These results suggest that endogenous protein kinase activity, specifically MLCK activity, regulates GABA, but not glutamate release, onto medium spiny neurons in the nucleus accumbens.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA.
authors.forename: Ajithkumar
authors.initials: A
authors.lastname: Warrier
authors.forename: Gregory O
authors.initials: GO
authors.lastname: Hjelmstad
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine