Cerebellar GABA B receptors modulate function of GABA A receptors

Interactions between GABA A and GABA B receptors were studied using muscimol‐stimulated uptake of 36 Cl − by membrane vesicles from mouse cerebellum. Baclofen inhibited muscimol‐stimulated 36 Cl − uptake and this action was more pronounced with longer flux times (30 vs. 3 s) and after predesensitization of GABA A receptors. Baclofen also inhibited 36 Cl − flux by cortical membranes but was more effective with cerebellar preparations. The action of baclofen was stereoselective, calcium‐dependent, and blocked by the GABA B 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 Ba 2+ did not affect the action of baclofen. The results show that activation of GABA B receptors can inhibit the function of GABA A receptors and suggest that this action involves either a nondesensitizing subtype of GABA A 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 GABA A receptor by protein kinase C.—Hahner, L.; McQuilkin, S.; Harris, R. A. Cerebellar GABA B receptors modulate function of GABA A receptors. FASEB J. 5: 2466–2472; 1991.