Nitric oxide inhibits the pannexin 1 channel through a cGMP-PKG dependent pathway. 2015

V Poornima, and Sirisha Vallabhaneni, and Mohona Mukhopadhyay, and Amal Kanti Bera
Department of Biotechnology, Bhupat & Jyoti Mehta School of BioSciences, Indian Institute of Technology Madras, Sardar Patel Road, Chennai, Tamil Nadu 600036, India.

Nitric oxide (NO), a major gaseous signaling molecule, modulates several ion channels and receptors. Here we show that NO attenuates pannexin 1 (Panx1) mediated currents in HEK-293 cells. NO exerts its effect by activating a cGMP-protein kinase G (PKG) dependent pathway. NO donors, sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO), reduced Panx1 currents by 25-41%. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase (sGC), blocked the inhibition completely, whereas sGC activator YC-1 mimicked the effect of NO, suggesting the involvement of a cGMP dependent pathway. Supporting this, NO had no effect in the presence of the PKG inhibitor, KT5823. Further, immuno-precipitated Panx1 was recognized by an anti-phosphoserine antibody in Western blot. Phosphorylation was enhanced significantly when cells were treated with SNP. The target for phosphorylation is possibly Ser 206 of Panx1, as its mutation to Ala completely abolished the NO mediated inhibition.

UI MeSH Term Description Entries
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017630 Connexins A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. Connexin,Connexin Complex Proteins,Gap Junction Proteins,Gap Junction Channel Proteins,Gap Junction Protein,Junction Protein, Gap,Junction Proteins, Gap
D057809 HEK293 Cells A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5. 293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell
D017869 Cyclic GMP-Dependent Protein Kinases A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins. Guanosine Cyclic Monophosphate-Dependent Protein Kinase,Guanosine Cyclic Monophosphate-Dependent Protein Kinases,cGMP-Dependent Protein Kinase,cGMP-Dependent Protein Kinases,Cyclic GMP-Dependent Protein Kinase,G-Kinase,G-Kinases,Guanosine Cyclic 3',5'-Phosphate-Dependent Protein Kinase,Protein Kinase G,Cyclic GMP Dependent Protein Kinase,Cyclic GMP Dependent Protein Kinases,G Kinase,G Kinases,Guanosine Cyclic 3',5' Phosphate Dependent Protein Kinase,Guanosine Cyclic Monophosphate Dependent Protein Kinase,Guanosine Cyclic Monophosphate Dependent Protein Kinases,Kinase, cGMP-Dependent Protein,Kinases, cGMP-Dependent Protein,Protein Kinase, cGMP-Dependent,Protein Kinases, cGMP-Dependent,cGMP Dependent Protein Kinase,cGMP Dependent Protein Kinases

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