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)

A putative, Na(+)-dependent Mg(2+) transport pathway controls the intracellular free Mg(2+) concentration ([Mg(2+)](i)) in various mammalian cells. The characteristics of this Mg(2+) transport pathway have not been clarified. Herein, we examined the regulatory mechanism of Na(+)-dependent Mg(2+) efflux in renal epithelial NRK-52E cells. Mg(2+) removal from the extracellular bathing solution induced an Na(+)-dependent [Mg(2+)](i) decrease in Mg(2+) (5 mM)-loaded cells but not in control cells. Amiloride inhibited the [Mg(2+)](i) decrease in a dose-dependent manner (IC(50) = 3 microM). Similarly, atomic absorption spectrophotometry showed that Mg(2+) removal decreased intracellular Mg(2+) content, while it increased Na(+) content. Calphostin C (1 microM), a protein kinase C inhibitor, and genistein, a tyrosine kinase inhibitor (10 microM), blocked the [Mg(2+)](i) decrease. The [Mg(2+)](i) decrease was accompanied by an increase in intracellular nitric oxide (NO) and cyclic GMP contents. (E)-4-methyl-2-[(E)-hydoxyimino]-5-nitro-6-methoxy-3-hexenamide (0.1 mM), an NO donor, and 8-bromo-cyclic GMP (0.1 mM), a membrane-permeable cyclic GMP analogue, accelerated the [Mg(2+)](i) decrease. In contrast, N(G)-monomethyl-L-arginine (L-NMMA, 0.1 mM), an NO competitive inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 microM), an NO-sensitive guanylate cyclase inhibitor, significantly blocked the [Mg(2+)](i) decrease. These results indicate that a decrease in extracellular Mg(2+) concentration induces the production of NO and cyclic GMP, which leads to the up-regulation of Na(+)-dependent Mg(2+) efflux.
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PMID:Up-regulation of Na+-dependent Mg2+ transport by nitric oxide and cyclic GMP pathway in renal epithelial cells. 1223 82

Atrial natriuretic peptide, besides its role in the regulation of volume homeostasis, has been noted to exert cytoprotective effects in several cell types from hypoxia. The present study was performed to explore the effect of ANP on high glucose-activated transforming growth factor-beta1 (TGF-beta1), Smad and collagen synthesis in renal proximal epithelial cells. Cultured NRK-52E cells were divided into five groups: (1) normal glucose (5.5 mM), (2) high glucose (35 mM), (3) D-mannitol (29.5 mM), (4) high glucose plus ANP (10(-6)-10(-9) M), and (5) high glucose plus ANP (10(-6) M) and guanylate cyclase inhibitor LY83583 (10(-7) M) groups. Messenger RNA levels of TGF-beta1, Smad2, and collagens were measured by RT-PCR. ELISA, immunocytochemistry and Western blotting were used to detect protein levels of TGF-beta1, Smad2, phospho-Smad 2/3 and collagen type 1. We found high glucose to significantly increase mRNA levels of TGF-beta1, Smad 2, collagen types I and III and protein levels of TGF-beta1, phospho-Smad 2/3 and collagen type 1, but mannitol did not affect their expression. The addition of ANP significantly attenuated high glucose-enhanced mRNA and protein levels of TGF-beta1, Smad and collagens. LY83583 blocked the influence of ANP on high glucose-activated TGF-beta1, Smad and collagen synthesis. This is the first study to demonstrate that activation of TGF-beta1, Smad and collagen synthesis stimulated by high glucose can also be inhibited by exogenous ANP in renal tubular epithelial cells.
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PMID:Atrial natriuretic peptide attenuates high glucose-activated transforming growth factor-beta, Smad and collagen synthesis in renal proximal tubular cells. 1796 May 94