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)

Nitric oxide and cGMP influence plasticity of nociceptive processing in spinal cord. However, effectors for cGMP have not been identified in sensory pathways. We now demonstrate that cGMP-dependent protein kinase I (cGKl) occurs in the DRGs at levels comparable to that in cerebellum, the richest source of cGKl in the body. Immunohistochemical studies reveal that cGKl is concentrated in a subpopulation of small- and medium-diameter DRG neurons that partially overlap with substance P and calcitonin gene-related polypeptide containing cells. During development, cGKl expression throughout the embryo is essentially restricted to sensory neurons and to the spinal floor and roof plates. Neuronal nitric oxide synthase (nNOS) is coexpressed with cGKl in sensory neurons during embryonic development and after peripheral nerve axotomy. The primary target for cGKl in cerebellum, G-substrate, is not present in developing, mature, or regenerating sensory neurons, indicating that other proteins serve as effectors for cGKl in sensory processing. These data establish sensory neurons as a primary locus for cGMP actions during development and suggest a role for cGKl in plasticity of nociception.
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PMID:cGMP-dependent protein kinase in dorsal root ganglion: relationship with nitric oxide synthase and nociceptive neurons. 862 52

Acid-sensing ion channels (ASICs) are a class of ion channels activated by extracellular protons and are believed to mediate the pain caused by tissue acidosis. Although ASICs have been widely studied, little is known about their regulation by inflammatory mediators. Here, we provide evidence that nitric oxide (NO) potentiates the activity of ASICs. Whole-cell patch-clamp recordings were performed on neonatal rat cultured dorsal root ganglion neurons and on ASIC isoforms expressed in CHO cells. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) potentiates proton-gated currents in DRG neurons and proton-gated currents in CHO cells expressing each of the acid-sensitive ASIC subunits. Modulators of the cGMP/PKG pathway had no effect on the potentiation, but in excised patches from CHO cells expressing ASIC2a, the potentiation could be reversed by externally applied reducing agents. NO therefore has a direct external effect on the ASIC ion channel, probably through oxidization of cysteine residues. Complementary psychophysiological studies were performed using iontophoresis of acidic solutions through the skin of human volunteers. Topical application of the NO donor glyceryl trinitrate significantly increased acid-evoked pain but did not affect heat or mechanical pain thresholds. ASICs may therefore play an important role in the pain associated with metabolic stress and inflammation, where both tissue acidosis and a high level of NO are present.
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PMID:Modulation of acid-sensing ion channel activity by nitric oxide. 1804 19