Article date: 1991/7/1
PubMed ID: 1648524
Journal name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (ISSN: 0892-6638)
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-gamma-S but not by GDP-beta-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 or 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.
Author List: Hahner L, McQuilkin S, Harris R A
Publication Types: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Estrenes; Pyrrolidinones; Receptors, GABA-A; Tetraethylammonium Compounds; guanosine 5'-O-(1-thiotriphosphate); 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; Barium; Muscimol; Guanosine 5'-O-(3-Thiotriphosphate); Chlorine; Tetraethylammonium; Type C Phospholipases; Baclofen; Calcium; 2-hydroxysaclofen;
Mesh terms: Animals; Baclofen/analogs & derivatives; Barium/pharmacology; Calcium/metabolism; Cells, Cultured; Cerebellum/metabolism; Cerebral Cortex/metabolism; Chlorine/pharmacokinetics; Dose-Response Relationship, Drug; Estrenes/pharmacology; Guanosine 5'-O-(3-Thiotriphosphate)/analogs & derivatives; In Vitro Techniques; Mice; Mice, Inbred ICR; Muscimol/pharmacology; Pyrrolidinones/pharmacology; Receptors, GABA-A/physiology; Tetraethylammonium; Tetraethylammonium Compounds/pharmacology; Time Factors; Type C Phospholipases/antagonists & inhibitors;