Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preincubation of guinea pig tracheas with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 120 microM) resulted in a significant upward shift of the histamine concentration-response curve with a concomitant inhibition of prostaglandin E2 production. Preincubation of the preparations with a 5-lipoxygenase inhibitor (AA-861, 2-(12-hydroxy-5,10-dodecadiynyl)-3,5,6-trimethyl-p-benzoquinone) or a leukotriene C4,D4,E4 receptor antagonist (FPL 55712, sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propoxy]-4-oxo-8- propyl-4H-1-benzopyran-2-carboxylate) totally blocked the L-NAME-induced tracheal hyperresponsiveness. A shift from cyclo-oxygenase to lipoxygenase products, in particular leukotrienes, is likely to be responsible for the L-NAME-induced tracheal hyperresponsiveness.
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PMID:Leukotrienes mediate tracheal hyperresponsiveness after nitric oxide synthesis inhibition. 856 26

1. The role of nitric oxide (NO) in the acid secretory response of the rat stomach following damage was investigated. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and the potential difference (PD), luminal pH, acid and HCO3- responses were measured before and after the mucosal exposure to 20 mM taurocholate (TC) for 30 min, with or without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME). 2. Exposure of the stomach to TC caused a reduction of PD, a decrease of acid secretion and an increase in luminal HCO-. Pretreatment with L-NAME did not affect such PD and HCO3- responses, but completely attenuated the decreased acid secretory response and rather enhanced this secretion. 3. These effects of L-NAME were significantly antagonized by the co-administration of L-arginine but not D-arginine. The enhanced acid secretory response in the presence of L-NAME was significantly inhibited by prior administration of cimetidine or FPL-52694 (a mast-cell stabilizer). 4. The mucosal exposure to TC significantly decreased the number of mucosal mast cells and increased the luminal histamine output. 5. Damage in the stomach may activate the histamine-dependent acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, although the latter effect overcomes the former, resulting in a decrease of acid secretion. L-NAME unmasks the stimulation of acid secretion by suppressing the inhibitory pathway.
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PMID:Stimulation of acid secretion in rat stomach following exposure to taurocholate in the presence of the nitric oxide synthase inhibitor. 884 89

The present study was performed to investigate the mechanism underlying the acid stimulatory response in the stomach after damage under the inhibition of nitric oxide (NO) production by N(G)-nitro-L-arginine methyl ester (L-NAME). A rat stomach was mounted in an ex vivo chamber, perfused with saline, and the potential difference (PD) and acid secretion were measured before and after the application of 20 mM taurocholate (TC) for 30 min. Exposure of the stomach to TC caused a PD reduction and a decrease of acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly enhanced the acid secretion in the stomach after damage with TC, without any effect on the PD response. This effect of L-NAME was antagonized by simultaneous administration of L-arginine but not D-arginine. The luminal appearance of NO was significantly increased in the stomach after exposure to TC, and this change was completely blocked in the presence of L-NAME or when EGTA was applied together with TC. The enhanced acid secretory response to TC in the presence of L-NAME was inhibited by pretreatment with cimetidine, FPL-52694 (a mast cell stabilizer), or spantide (a substance P antagonist) or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of metachromatically staining cells in the stomach, and these changes were also significantly prevented by FPL-52694, spantide, or sensory deafferentation. These results suggest that 1) damage in the stomach may activate the acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion, 2) the acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cell which may interact with capsaicin-sensitive sensory nerves, and 3) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.
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PMID:Mechanism of acid secretory changes in rat stomach after damage by taurocholate: role of nitric oxide, histamine, and sensory neurons. 907 52

The stomach normally responds to mucosa-damaging agents by decreasing acid secretion, but this acid response turn from "inhibition" into "stimulation" when the production of nitric oxide (NO) is inhibited by NG-nitro-L-arginine methyl ester (L-NAME). We investigated the mechanism underlying stimulation of acid secretion in the stomach after damage with taurocholate (TC) in the presence of L-NAME. A rat stomach was mounted in an ex vivo chamber and perfused with saline, and the potential difference (PD), luminal pH, and acid secretion were measured before and after application of 20 mM TC for 30 min. Exposure of the stomach to TC caused a reduction in PD, an increase in luminal pH, and a decrease in acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly increased secretion after damage with TC, without any effect on PD. This effect of L-NAME was antagonized by co-administration of L-arginine but not D-arginine. The luminal appearance of NO was also increased after exposure of the stomach to TC, a phenomenon completely blocked by L-NAME, or when EGTA was applied together with TC. The enhanced acid secretory response in the presence of L-NAME was inhibited by prior administration of cimetidine, FPL-52694 (a mast cell stabilizer), spantide (a substance P antagonist), or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 or sensory neuronal ablation. These results suggest that (a) damage in the stomach may activate acid stimulation in addition to an NO-dependent inhibitory mechanism but that the latter effect overcomes the former, resulting in a decrease in acid secretion, (b) acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cells, a process that may interact with capsaicin-sensitive sensory nerves, and (c) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.
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PMID:Nitric oxide, histamine, and sensory nerves in the acid secretory response in rat stomach after damage. 947 25

We examined the effect of NO synthase inhibitor on the functional and ulcerogenic responses to aspirin (ASA) in rat stomach. The animals were given ASA (20-80 mM) orally with or without HCl (10-50 mM) and killed 2 h later. NG-nitro-L-arginine methyl ester (L-NAME) was given i.v. 5 min before aspirin. In the functional study, a rat stomach was mounted on an ex vivo chamber under urethane anesthesia, perfused with saline, and transmucosal potential difference (PD), luminal pH, acid secretion and mucosal blood flow (GMBF) were measured simultaneously. ASA alone caused gastric damage in a dose-related manner; mostly nonhemorrhagic lesions. Pretreatment with L-NAME worsened such lesions and caused severe hemorrhagic lesions. Coadministration of HCl with ASA also potentiated gastric lesions in a concentration-dependent manner, changing nonhemorrhagic into hemorrhagic damage, and the worsening effect of L-NAME disappeared when 80 mM ASA was given together with HCl at >20 mM. In chambered stomachs, the mucosal application of ASA (80 mM, 30 min) caused a marked reduction in PD and a slight decrease in acid secretion, with minimal change in GMBF. L-NAME blocked the reduced acid response following ASA and caused stimulation of acid secretion with no effect on PD and GMBF. These effects of L-NAME were all antagonized by coadministration of L-arginine and significantly mitigated by sensory deafferentation or pretreatment with cimetidine or FPL-52694. These results suggest that (1) intragastric administration of ASA causes a release of NO, which reduces the development of hemorrhagic lesions by decreasing acid secretion, and (2) L-NAME worsens gastric damage by increasing acid secretion in ASA-treated stomachs, the process being dependent on endogenous histamine and sensory neurons.
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PMID:Role of nitric oxide in pathogenesis of aspirin-induced gastric mucosal damage in rats. 969 99

The present article overviews the regulatory mechanism of acid secretion in the stomach after damage with taurocholate (TC), one of the bile acids. Mucosal exposure of a rat stomach to 20 mmol/L TC for 30 min caused a decrease of acid secretion with a concomitant increase in nitric oxide (NO) and prostaglandin (PG) E2 (PGE2) as well as Ca2+ in the luminal contents. Prior administration of N(G)-nitro-L-arginine methyl ester (L-NAME), as well as indomethacin, significantly attenuated the reduction of acid secretion by TC and acid secretion was even increased in the presence of L-NAME. The acid stimulatory effect of L-NAME in the damaged stomach was not mimicked by aminoguanidine and was antagonized by co-administration of L-arginine but not D-arginine. Increased NO release in the damaged stomach was suppressed by pretreatment with L-NAME or co-application of EGTA and the latter also inhibited the increase in luminal Ca2+. The enhanced acid secretory response in the presence of L-NAME was also inhibited by cimetidine, FPL-52694 (a mast cell stabilizer) or sensory deafferentation. Mucosal exposure to TC caused an increase in luminal histamine output, together with a decrease in the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 and sensory deafferentation and were also partly suppressed by indomethacin. In addition, the acid stimulatory action of L-NAME in the damaged stomach was significantly mitigated when indomethacin was administered together with L-NAME. We conclude that: (i) damage in the stomach may activate acid a stimulatory pathway in addition to a PG-, NO- and Ca2+-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion; (ii) acid stimulation in the damaged stomach is mediated by histamine released from the mucosal mast cell, a process interacting with capsaicin-sensitive sensory nerves; (iii) the increase in luminal Ca2+ plays a role in increasing NO production and, hence, in regulating acid secretion; and (iv) PG may have a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect, probably through enhancing the release of mucosal histamine.
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PMID:Regulatory mechanism of acid secretion in the damaged stomach: role of endogenous nitric oxide. 1075 19

The objective of this study was to determine whether arachidonate metabolites are involved in the vasoconstrictive effects of angiotensin II in rats. In the isolated perfused heart, dexamethasone (4 mg/kg) significantly suppressed the maximal decreases in coronary flow induced by angiotensin II and vasopressin (reference drug). In the heart, the nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1 muM) markedly suppressed the angiotensin II-induced decreases in coronary flow. NDGA (10 muM) inhibited both angiotensin II- and methoxamine- (reference drug) induced contractions in aortic rings with (in the presence of L-NAME) and without endothelium. In the heart, the leukotriene synthesis inhibitor MK-886 (0.3 muM) significantly reduced the maximal effects to angiotensin II, but the leukotriene antagonist FPL 55712 (0.1 and 0.3 muM) had no effect. We conclude that in the isolated perfused rat heart angiotensin II-induced decreases in coronary flow are in part mediated by Hpoxygenase products, which might be derived from the 5-Hpoxygenase pathway, but are probably not leukotrienes. Furthermore, endothelium independent Hpoxygenase products mediate part of the contractile responses to angiotensin II in the isolated rat aorta.
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PMID:Role of lipoxygenase products in the effects of angiotensin II in the isolated aorta and perfused heart of the rat. 1847 74