2172778

gamma-Aminobutyric acidA receptor desensitization in mice spinal cord cultured neurons: lack of involvement of protein kinases A and C.

Article date: 1990/11/1

PubMed ID: 2172778

Journal name: Molecular pharmacology (ISSN: 0026-895X)

ABSTRACT

Desensitization of the gamma-aminobutyric acidA (GABAA) receptor was studied in cultured mammalian spinal cord neurons, using a GABA-induced 36Cl-influx assay. GABAA receptor agonists such as GABA and muscimol produced desensitization of GABAA receptor-gated Cl- channels. The ability of GABA to induce desensitization was time and concentration dependent and reversible. Involvement of protein kinase A in the desensitization phenomenon was studied by using activators of adenylate cyclase (forskolin analogs) and membrane-permeant analogs of cyclic AMP (8-bromo-cAMP and dibutyryl-cAMP). Both active forskolin and the inactive forskolin analog 1,9-dideoxyforskolin decreased GABA-induced 36Cl- influx alone, as well as when preincubated in conjunction with GABA. The effect of forskolin analogs appears to be nonspecific and unrelated to generation of cyclic AMP. GABA-induced 36Cl- influx was also inhibited directly by 8-bromo-cAMP, dibutyryl-cAMP, and cAMP. Furthermore, the protein kinase A inhibitor H-8 did not reverse the effect of cAMP analogs on the inhibition of GABA-induced 36Cl- influx. Taken together, these results suggest that cAMP analogs inhibit GABA-induced 36Cl- influx by acting via an extracellular site. The inability of the active phorbol ester to modify GABA-induced desensitization rules out the involvement of protein kinase C in the GABA receptor desensitization. These results suggest that protein kinases A and C are not involved in GABAA receptor desensitization in mouse spinal cord cultured neurons.

Author List: Ticku M K, Mehta A K

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Chloride Channels; Membrane Proteins; Protein Kinase Inhibitors; Receptors, GABA-A; Colforsin; gamma-Aminobutyric Acid; Protein Kinases; Protein Kinase C;

Mesh terms: Animals; Cells, Cultured/drug effects; Chloride Channels; Colforsin/pharmacology; Female; Male; Membrane Proteins/drug effects; Mice; Mice, Inbred C57BL; Neurons/drug effects; Protein Kinase C/metabolism; Protein Kinase Inhibitors; Protein Kinases/metabolism; Receptors, GABA-A/drug effects; Spinal Cord/drug effects; gamma-Aminobutyric Acid/pharmacology;

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