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)

We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1), Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on the mechanical performance of the isolated and perfused working eel (Anguilla anguilla) heart. Under basal conditions, the three peptides decreased stroke volume (SV) and stroke work (SW), thus exerting negative inotropism. The VS-1-mediated negative inotropism was abolished by exposure to inhibitors of either Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine, tetraethylammonium, glibenclamide) channels, while it required an intact endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger, we demonstrated the obligatory role of NO signaling in mediating the vasostatin response. Pretreatment with either a specific inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated inotropism, indicating the cGMP-PKG component as a crucial target of NO signaling. Of note, VS-1 was effective in counteracting the adrenergic (Isoproterenol and Phenylephrine)-mediated positive inotropism. These findings provide the first evidence that vasostatins exert cardiotropic action in fish, thus suggesting their long evolutionary history as well as their species-specific mechanisms of action.
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PMID:Influence of vasostatins, the chromogranin A-derived peptides, on the working heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action. 1547 32

Cyclic guanosine monophosphate (cGMP) has been recently shown to modulate in vitro capacitation of mammalian spermatozoa, but the mechanisms through which it influences sperm functions have not been clarified. There are at least two targets of cGMP, cyclic nucleotide-gated (CNG) channels and cGMP-dependent protein kinase (PKG), involved in several physiological events in mammalian spermatozoa. It has been suggested that CNG channels allow the influx of Ca(2+) to cytoplasm during capacitation, whereas PKG could trigger a phosphorylation pathway which might also, indirectly, mediate calcium entry. Using the patch-clamp technique in whole-cell configuration, we showed how l-cis-Diltiazem (a CNG-channel inhibitor) and KT5823 (a PKG inhibitor) decreased significantly the amplitude of macroscopic ion currents in a dose-response manner, and decreased in vitro capacitation. The inhibition of CNG channels completely abolishes the Ca(2+) influx induced by cyclic nucleotides in mouse spermatozoa. This work suggests that the downstream cGMP pathway is required in mammalian sperm capacitation and the mechanisms involved include CNG channels and PKG, highlighting these molecules as important therapeutic targets for infertility treatments or to develop new male contraceptives.
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PMID:Capacitation and Ca(2+) influx in spermatozoa: role of CNG channels and protein kinase G. 2429 81