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)

Ghrelin, a recently discovered 28-aa peptide, stimulates GH release through a mechanism involving PLC- and cAMP-related signaling pathways. Recently, nitric oxide (NO) and its mediator, cGMP, have been shown to be required for the response of somatotropes to various regulators (GHRH, somatostatin, leptin). Here, we explore the possible role of the NO synthase (NOS)/NO/guanylate cyclase (GC)/cGMP signaling pathway in ghrelin-induced GH release from cultured pig somatotropes using blockers or activators of this route.
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PMID:Ghrelin induces growth hormone (GH) secretion via nitric oxide (NO)/cGMP signaling. 1589 Oct 86

Ghrelin regulates bone formation and osteoblast proliferation, but the detailed signaling pathway for its action on osteoblasts remains unclear. In human osteoblastic TE85 cells, we observed the effects and intracellular signaling pathway of ghrelin on cell proliferation using BrdU incorporation method. Ghrelin, at 10(-10)-10(-8) M concentration, significantly increased BrdU incorporation into TE85 cells. The action of ghrelin was inhibited by D: -Lys3-GHRP-6, a selective antagonist of GHS-R. Nitric oxide (NO) scavenger hemoglobin and the NO synthase inhibitor NAME eliminated the stimulatory action of ghrelin on proliferation, while NO donor SNAP and NO synthase substrate L-AME stimulated proliferation of osteoblastic TE85 cells. The cGMP analogue, 8-Br-cGMP, stimulated TE85 cell proliferation, and ghrelin did not enhance proliferation in the presence of 8-Br-cGMP. Inhibition of cGMP production by the guanylate cyclase inhibitor prevented ghrelin-induced osteoblastic TE85 cell proliferation. In conclusion, ghrelin stimulates proliferation of human osteoblastic TE85 cells via intracellular NO/cGMP signaling pathway.
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PMID:Ghrelin stimulates proliferation of human osteoblastic TE85 cells via NO/cGMP signaling pathway. 1895 75

The hypothesis is that the ghrelin signal pathway consists of new participants including a local second mediator in human mesenteric arteries. The contractile force of isometric artery preparations was measured using a wire-myograph. Whole-cell patch clamp experiments were performed on freshly isolated single smooth muscle cells from the same tissue. After the addition of ghrelin (100 nmol) the outward potassium currents conducted through iberiotoxin-sensitive calcium-activated potassium channels with a large conductance were almost entirely abolished. The effect of ghrelin on potassium currents was insensitive to selective inhibitors of cAMP-dependent protein kinase and soluble guanylate cyclase, but was eliminated in the presence of des-octanoyl ghrelin and O-(octahydro-4,7-methano-1H-inden-5-yl) carbonopotassium dithioate (D-609). Ghrelin dose-dependently increased the force of contraction of native, endothelium-denuded and mostly of endothelium-denuded and treated with tetrodotoxin human mesenteric arteries preconstricted with 1 nmol endothelin-1. This effect of ghrelin was blocked when the bath solution contained 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), D-609, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203x), pertussis toxin, 2-aminoethyl diphenylborinate (2-APB), indomethacin, (5Z,13E)-(9S,11S,15R)-9,15,Dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20,pentanor-5,13-prostadienoic acid (AL-8810) - a non-selective prostanoid receptor antagonist, 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazolo (SC-560) - a selective cyclooxygenase 1 inhibitor, ozagrel - a selective thromboxane A(2) synthase inhibitor or T prostanoid receptor antagonist GR32191B. It is concluded that ghrelin increases the force of contraction of human mesenteric arteries by a novel mechanism that involves Src kinase, mitogen-activated protein kinase kinase (MEK), cyclooxygenase 1 and T prostanoid receptor agonist, most probably thromboxane A(2).
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PMID:Ghrelin signaling in human mesenteric arteries. 2081 65