Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a potent neuromodulator in the CNS and PNS. At the frog neuromuscular junction (nmj), exogenous application of NO reduces neurotransmitter release, and NO synthases (NOSs), the enzymes producing NO, are present at this synapse. This work aimed at studying the molecular mechanisms by which NO modulates synaptic efficacy at the nmj using electrophysiological recordings and Ca(2+)-imaging techniques. Bath application of the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside decreased end plate potential (EPP) amplitude as well as the frequency of miniature EPPs but not their amplitude. Ca(2+) responses elicited in presynaptic terminals by single action potentials were unaffected by NO, but responses evoked by a short train of stimuli were increased. Tonic endogenous production of NO was observed as suggested by the increase in EPP amplitude by bath application of the NO scavenger hemoglobin and the neuronal NOS inhibitor 3-bromo-7-nitroindazole sodium salt. A soluble guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY-83583), increased EPP amplitude and occluded the effects of the NO donor, suggesting that NO acts via a cGMP-dependent mechanism. High-frequency-induced depression was reduced in the presence of the NO scavenger but not by LY-83583. However, adenosine-induced depression was significantly reduced after bath perfusion of SNAP and in the presence of LY-83583. Our results indicate that NO regulates transmitter release and adenosine-induced depression via a cGMP-dependent mechanism that occurs after Ca(2+) entry and that high-frequency-induced synaptic depression is regulated by NO in a cGMP-independent manner.
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PMID:Differential frequency-dependent regulation of transmitter release by endogenous nitric oxide at the amphibian neuromuscular synapse. 1116 Mar 78

Satellite glial cells (SGCs) tightly envelop the perikarya of primary sensory neurons in peripheral ganglion and are identified by their morphology and the presence of proteins not found in ganglion neurons. These SGC-unique proteins include the inwardly rectifying K(+) channel Kir4.1, the connexin-43 (Cx43) subunit of gap junctions, the purinergic receptor P2Y4 and soluble guanylate cyclase. We also present evidence that the small-conductance Ca(2+)-activated K(+) channel SK3 is present only in SGCs and that SGCs divide following nerve injury. All the above proteins are involved, either directly or indirectly, in potassium ion (K(+)) buffering and, thus, can influence the level of neuronal excitability, which, in turn, has been associated with neuropathic pain conditions. We used in vivo RNA interference to reduce the expression of Cx43 (present only in SGCs) in the rat trigeminal ganglion and show that this results in the development of spontaneous pain behavior. The pain behavior is present only when Cx43 is reduced and returns to normal when Cx43 concentrations are restored. This finding shows that perturbation of a single SGC-specific protein is sufficient to induce pain responses and demonstrates the importance of PNS glial cell activity in the pathophysiology of neuropathic pain.
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PMID:Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain. 1856 96