Nitric oxide depresses GABA(A) receptor function via coactivation of cGMP-dependent kinase and phosphodiesterase

Eric M. Wexler, Patric K. Stanton, Scott Nawy

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Nitric oxide (NO) is thought to play an essential role in neuronal processing, but the downstream mechanisms of its action remain unclear. We report here that NO analogs reduce GABA-gated currents in cultured retinal amacrine cells via two distinct, but convergent, cGMP-dependent pathways. Either extracellular application of the NO-mimetic S-nitroso-N- acetylpenicillamine (SNAP) or intracellular perfusion with cGMP depressed GABA currents. This depression was partially blocked by a pseudosubstrate peptide inhibitor of cGMP-dependent protein kinase (PKG), suggesting both PKG-dependent and independent actions of cGMP. cAMP-dependent protein kinase (PKA) is known to enhance retinal GABA responses. 8-Bromoinosine 3',5'- cyclic monophosphate (8Br-cIMP), which activates a type of cGMP-stimulated phosphodiesterase that hydrolyzes cAMP, also significantly reduced GABA currents. 1-Methyl-3-isobutylxanthine (IBMX), a nonspecific phosphodiesterase (PDE) inhibitor, blocked both the action of 8Br-cIMP and the portion of SNAP- induced depression that was not blocked by PKG inhibition. Our results suggest that NO depresses retinal GABA(A) receptor function by simultaneously upregulating PKG and downregulating PKA.

Original languageEnglish (US)
Pages (from-to)2342-2349
Number of pages8
JournalJournal of Neuroscience
Issue number7
StatePublished - Apr 1 1998
Externally publishedYes


  • Amacrine
  • Culture
  • Guanylate cyclase
  • Nitric oxide
  • ODQ
  • PKG inhibitory peptide
  • Retina
  • SNAP

ASJC Scopus subject areas

  • General Neuroscience


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