γ-Aminobutyric acid(A) receptor desensitization in mice spinal cord cultured neurons: Lack of involvement of protein kinases A and C

M. K. Ticku, A. K. Mehta

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Desensitization of the γ-aminobutyric acid(A) (GABA(A)) receptor was studied in cultured mammalian spinal cord neurons, using a GABA-induced 36Cl- influx assay. GABA(A) receptor agonists such as GABA and muscimol produced desensitization of GABA(A) 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 GABA(A) receptor desensitization in mouse spinal cord cultured neurons.

Original languageEnglish (US)
Pages (from-to)719-724
Number of pages6
JournalMolecular pharmacology
Volume38
Issue number5
StatePublished - 1990
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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