Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of tumor necrosis factor-alpha (TNF-alpha) on the production of the vasoactive substances nitric oxide (NO) and endothelin-1 (ET-1) were investigated in cerebrovascular cells in culture. Bovine cerebral endothelial cells (BCEC) stained positively for NADPH-diaphorase/NO synthase activity and spontaneously produced nitrite, a stable NO oxidation product, which accumulated in the culture medium in a linear way for 48 h. Low concentrations of TNF-alpha (0.5-2 ng/ml) significantly enhanced nitrite production after a 24-h incubation. Higher concentrations or longer exposure times resulted in a cytotoxic effect that altered cell morphology, released lactate dehydrogenase (LDH) to the culture medium, and reduced the protein content. Dexamethasone, but not the NO synthase inhibitor N-iminoethyl-L-ornithine (L-NIO), prevented the cytotoxic effect of TNF-alpha in BCEC. TNF-alpha also significantly enhanced nitrite production in bovine cerebral smooth muscle cells (BCSMC). The enhancement was detected at all times between 8 and 72 h and at all concentrations tested (2-100 ng/ml). Signs of cytotoxicity were not observed in BCSMC after incubation with TNF-alpha. ET-1 was constitutively secreted by BCEC. The production of ET-1 was stimulated by thrombin. TNF-alpha enhanced the release of ET-1 in BCEC, and this enhancement was not modified by the simultaneous addition of interferon-gamma (IFN-gamma). BCSMC did not produce ET-1, either spontaneously or in the presence of TNF-alpha, IFN-gamma, or of both together.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of TNF-alpha on the production of vasoactive substances by cerebral endothelial and smooth muscle cells in culture. 759 52

Aims of this study were to functionally and histologically determine the localization of ganglia that distribute inhibitory nerves to the penile corpus cavernosum in dogs. In isolated corpus cavernosa from seven control dogs contracted with endothelin-1, transmural electrical stimulation (5 Hz for 40 s) elicited contractions which were reversed to relaxations by prazosin. The relaxation was abolished by NG-nitro-l-arginine (l-NNA), a nitric oxide (NO) synthase inhibitor, and restored by l-arginine. Parts of bilateral pelvic nerve plexuses running to the penis were surgically denervated in anesthetized three dogs, or the bilateral neuronal tissues close to the corpus cavernosum were removed for denervation in seven dogs. One week after the operation, the dogs were sacrificed. Denervation of pelvic plexus did not attenuate neurogenic relaxations, whereas denervation of the distal portion abolished the responses. In the tissues close to the corpus cavernosum excised for denervation, ganglia containing abundant nerve cells and fibers stained by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase method were histochemically detected. One week after the denervation, there were no NADPH diaphorase-positive nerve fibers in the trabecula of corpus cavernosum. It is concluded that neurogenic relaxations of canine corpus cavernosum are mediated by NO synthesized from l-arginine in nerve terminals, and this nerve is originated from ganglia located close to the corpus cavernosum but not directly from the pelvic nerve plexus.
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PMID:Influence of denervation on neurogenic inhibitory response of corpus cavernosum and nitric oxide synthase histochemistry. 1021 69

Nitric oxide (NO) has been found to modulate the response of rat, bovine and human adrenocortical cells to corticotropic factors. The aim of the present study was to investigate the possible involvement of NO in the control of corticosteroid secretion in the frog Rana ridibunda. Histochemical studies using the NADPH-diaphorase reaction and immunohistochemical labeling with antibodies against NO synthase (NOS) revealed that NOS is exclusively expressed in chromaffin cells. The NO donor sodium nitroprusside (SNP) and the NO synthase inhibitor Nw-nitro-L-arginine (L-NO(2)Arg) did not modify the spontaneous production of corticosterone and aldosterone by perifused adrenal slices. Similarly, L-NO(2)Arg had no effect on the secretory responses induced by ACTH, angiotensin II (AII) and endothelin-1 (ET-1). In contrast, SNP significantly inhibited the stimulatory effects of ACTH, AII and ET-1 on corticosterone and aldosterone secretion. These data provide the first evidence for a modulatory role of NO on adrenocortical cell activity in amphibians.
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PMID:Evidence for the involvement of nitric oxide in the control of steroid secretion by the frog adrenal gland. 1145 63

The development and progression of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits is associated with increases in inducible nitric oxide synthase (NOS2) and endothelin-1 (ET-1) immunoreactivity. In contrast, there is a reduction of immunoreactivity for neuronal NOS (NOS1) in aortic endothelial cells, but no change in endothelial NOS (NOS3) immunoreactivity. However, subendothelial macrophages and smooth muscle showed a different pattern of immunoreactivity of NADPH-diaphorase (NADPH-d), NOS2, ET-1, and NOS1. The lipid-rich macrophages in the intima were positively labeled for NADPH-d, NOS1, NOS2, NOS3, and ET-1. Smooth muscle cells in the subendothelium and the medial layers of the vascular wall were also positive for these markers. These results are consistent with the reduction of endothelium-dependent vasorelaxation that is known to occur during the development and progression of atherosclerosis in familial hypercholesterolemia. The data suggest a key role for vasoactive substances in the development of atherosclerosis.
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PMID:Atherosclerotic lesions are associated with increased immunoreactivity for inducible nitric oxide synthase and endothelin-1 in thoracic aortic intimal cells of hyperlipidemic Watanabe rabbits. 1150 96

Newborn rats received intraperitoneal injections of endothelin-1 in a daily dose of 5 x 10(-8)mol/kg 30 min after administration of NG-nitro-L-arginine methyl ester (9.3 x 10(-5)mol/kg intraperitoneally) from the 2nd to 6th day of life. NADPH diaphorase activity in epithelial and smooth muscle cells of the tracheobronchial system increased 24 h after the last treatment. In this period DNA synthesis underwent opposite changes, which included the inhibition of epithelial cell proliferation and stimulation of smooth muscle cell division. Intensification of free radical oxidation in the lung tissue was accompanied by inactivation of the antioxidant system.
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PMID:Effects of endothelin-1 on DNA synthesis and NADPH diaphorase activity in epithelial and smooth muscle cells of the tracheobronchial system in newborn albino rats after repeated treatment with NG-nitro-L-arginine methyl ester. 1236 Mar 40