Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 We investigated the neuritogenic action of nitric oxide (NO)-generating agents and their mechanisms of action in a subclone of rat pheochromocytoma, PC12h cells. 2 NO donors such as sodium nitroprusside (SNP, 0.05-1 microM), NOR1 (5-100 microM), NOR2 (5-20 microM), NOR3 (5-20 microM), NOR4 (5-100 microM), or S-nitroso-N-acetyl-DL-penicillamine (SNAP, 10-100 microM) significantly induced neurite outgrowth. 3 NOR4-induced neurite outgrowth was accompanied by expression of neurofilament 200 kDa subunit (NF200) protein, an axonal marker, and was significantly inhibited by an NO scavenger, a soluble GC inhibitor, and a PKG inhibitor: 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (carboxy-PTIO, 20-100 microM), 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 100 microM) and KT5823 (0.2-1 microM), respectively. 4 The intracellular cGMP concentration of cells was markedly increased by treatment with NOR4 (100 microM). 5 A mitogen-activated protein kinase (MAPK) kinase inhibitor, PD98059 (10-50 microM), abolished the NOR4-induced neurite outgrowth. In agreement with this observation, NOR4 did phosphorylate extracellular signal-regulated kinase (ERK) 1 and 2, substrates of MAPK kinase. 6 A membrane-permeable cGMP analog, 8-Br-cGMP (1 mM) also induced significant neurite outgrowth. The 8-Br-cGMP-induced neurite outgrowth was almost completely inhibited by both KT5823 (0.5 microM) and PD98059 (50 microM). Moreover, sustained ERK phosphorylation was observed in the 8-Br-cGMP-treated PC12h cells. 7 These results suggest that NO itself has the ability to induce neurite outgrowth and that NO-induced ERK activation involves the NO-cGMP-PKG signaling pathway in PC12h cells.
 ...
PMID:Fundamental role of nitric oxide in neuritogenesis of PC12h cells. 1611 90

We have recently demonstrated that nitric oxide (NO) produced by neuronal NO synthase (nNOS) in the spinal cord is involved in the maintenance of neuropathic pain. To clarify whether NO itself affected nNOS activity in the spinal cord as a retrograde messenger, we examined the involvement of the NO/cGMP signaling pathway in the regulation of nNOS activity by NADPH-diaphorase histochemistry. NO-generating agents NOR3 (t(1/2)=30min) and SNAP (t(1/2)=5h), but not NOR1 (t(1/2)=1.8min), significantly enhanced NADPH-diaphorase staining in the spinal cord. 8-Br-cGMP also enhanced it similar to that by NOR3, and 8-Br-cAMP and forskolin, an activator of adenylate cyclase, enhanced it moderately. NOR1 and NOR3 markedly increased the cGMP level in the spinal cord. The enhancement of NADPH-diaphorase staining by NOR3 was significantly inhibited by CPTIO, an NO scavenger, ODQ, a soluble guanylate cyclase inhibitor, and KT5823, an inhibitor of cGMP-dependent protein kinase. Additionally, the NOR3-enhanced nNOS activity was completely inhibited by NMDA antagonists MK-801 and d-AP5, partially by the GluRepsilon2-selective antagonist CP-101,606, and was attenuated in GluRepsilon1(-/-) and GluRepsilon1(-/-)/epsilon4(-/-) mice. These results suggest that NO may regulate nNOS activity as a retrograde messenger in the spinal cord via activation of NMDA receptor containing GluRepsilon1 and GluRepsilon2 subunits.
 ...
PMID:Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors. 1754 18