Cerebellar GABA B receptors modulate function of GABA A receptors

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Abstract
Interactions between GABAA and GABAB receptors were studied using muscimol-stimulated uptake of 36Cl− by membrane vesicles from mouse cerebellum. Baclofen inhibited muscimol-stimulated 36Cl− uptake and this action was more pronounced with longer flux times (30 vs. 3 s) and after predesensitization of GABAA receptors. Baclofen also inhibited 36Cl− flux by cortical membranes but was more effective with cerebellar preparations. The action of baclofen was stereoselective, calcium-dependent, and blocked by the GABAB receptor antagonist 2-OH-saclofen. It was mimicked by GTP-γ-S but not by GDP-β-S, which suggests that baclofen may be acting via a G protein. The action of baclofen was inhibited by U73122, an inhibitor of phospholipase C. However, the potassium channel blockers tetraethylammonium or Ba2+ did not affect the action of baclofen. The results show that activation of GABAB receptors can inhibit the function of GABAA receptors and suggest that this action involves either a nondesensitizing subtype of GABAA receptor or the rate of recycling of desensitized to nondesensitized receptors. We speculate that this action of baclofen results from activation of phospholipase C and phosphorylation of a subtype of GABAA receptor by protein kinase C.—Hahner, L.; McQuilkin, S.; Harris, R. A. Cerebellar GABAB receptors modulate function of GABAA receptors. FASEB J. 5: 2466–2472; 1991.

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