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GABAC-receptor stimulation activates cAMP-dependent protein kinase via A-kinase anchoring protein 220.

Authors: Yang, L  Nakayama, Y  Hattori, N  Liu, B  Inagaki, C 
Citation: Yang L, etal., J Pharmacol Sci. 2008 Apr;106(4):578-84. Epub 2008 Apr 3.
Pubmed: (View Article at PubMed) PMID:18385542

In our previous study, anti-apoptotic effects of GABA(C)-receptor stimulation was suppressed by inhibitors of cAMP-dependent protein kinase (PKA), implying GABA(C) receptor-mediated PKA activation. The present study showed that GABA(C)-receptor stimulation with its agonist, cis-4-aminocrotonic acid (CACA), protected cultured hippocampal neurons from amyloid beta 25 - 35 (Abeta25 - 35) peptide-enhanced glutamate neurotoxicity. This protective effect of CACA was blocked by PKA inhibitors, KT 5720 and H-89, as well as a specific GABA(C)-receptor antagonist, (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA). To test the possibility of GABA(C) receptor-mediated PKA activation, association of GABA(C) receptor with A-kinase anchoring proteins (AKAPs) and effect of an AKAP antisense oligonucleotide on the PKA activation were examined in primary cultured rat hippocampal neurons. Stimulation of the cells with CACA-activated PKA was assessed by the phosphorylated PKA substrate (135 kDa) level. Specific antibodies raised against GABA(C)-receptor rho subunits precipitated each rho subunit, AKAP220, and PKA regulatory and catalytic subunits from rat brain lysates, suggesting that rho is associated with the AKAP220/PKA complex. Furthermore, antisense oligonucleotide of AKAP220 suppressed such GABA(C) stimulation-induced PKA activation, suggesting that GABA(C)-receptor stimulation activates PKA via AKAP220.


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RGD Object Information
RGD ID: 2312637
Created: 2009-08-26
Species: All species
Last Modified: 2009-08-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.