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

The influence of nitric oxide (NO) on hypnotic activity of diazepam, chlordiazepoxide and clonazepam was studied in mice. Administration of both non-selective NO synthase inhibitors: N(G)-nitro-L-arginine methyl ester (L-NAME), N(G)-nitro-L-arginine (L-NOARG) and selective NO synthase inhibitor 7-nitroindazole (7-NI) resulted in significant increase in the duration of diazepam-, chlordiazepoxide- and clonazepam-induced sleep. The effects of co-administration of the examined inhibitors with benzodiazepines were not changed by L-arginine, a substrate for NO formation. Administration of L-arginine alone had no effect on the duration of sleep induced by benzodiazepines. Methylene blue, the guanyl cyclase inhibitor, was able to increase the duration of benzodiazepine-induced sleep. These findings suggest that the cGMP/NO system may participate in hypnotic effects of benzodiazepines.
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PMID:Involvement of nitricoxidergic system in the hypnotic effects of benzodiazepines in mice. 1566 84

It has been reported that nitric oxide (NO) is involved in the relaxation mechanism of ginsenoside saponin in various smooth muscle in experimental animals. Although ginsenoside Rg(3) showed both endothelium-dependent and -independent component relaxation in vascular smooth muscle, the action mechanism of the relaxation of corporal muscle is not clear. We, thus, investigated the relaxation mechanism of ginsenoside Rg(3) using isolated canine corpus cavernosum. Ginsenoside Rg(3) concentration-dependently relaxed the canine corpus cavernosum that had been contracted by phenylephrine (PE), in which IC(50) was 1.68 x 10(-5) g/ml. Ginsenoside Rg(3) significantly (P < 0.05) potentiated acetylcholine (ACh)-induced relaxation in endothelium intact corpus cavernosum. Methylene blue (MB) but not N(omega)-nitro-L-arginine methylester (L-NAME) or ODQ (1H-[1,2,4]oxadiazol-[4,3-]quinoxsalin-1-one) modified the dose-response curve of ginsenoside Rg(3). Ginsenoside Rg(3) also significantly potentiated relaxation response to UV light in the presence of streptozotocin (STZ), which was almost completely (P < 0.01) blocked by ODQ. Ginsenoside Rg(3) concentration-dependently inhibited corporal phosphodiesterases (PDE), which resulted in increase of cyclic adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP) contents in corporal smooth muscles. MB inhibited the accumulation of cGMP but not cAMP by ginsenoside Rg(3). These results indicate that mechanism responsible for the relaxation by ginsenoside Rg(3) is not by stimulating endothelial nitric oxide synthase (eNOS) of the canine corporal smooth muscle but by increasing cyclic nucleotide levels through PDE inhibition.
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PMID:Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation. 1584 20

We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K+ channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K+ channels.
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PMID:Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats. 1611 30

Lactoferrin (LF) is a multifunctional protein that is widely found in milk, blood, and other biological fluids. In the present study, we investigated the possibility that LF may block a tolerance to morphine-induced analgesia in the mouse. The nociceptive effect of bovine milk-derived LF (bLF) was estimated in the mouse tail-flick test. Although an intraperitoneal (100 mg/kg) or an oral (300 mg/kg) administration of bLF did not show remarkable analgesia, a combination with intraperitoneal administration of morphine (3 mg/kg) strikingly enhanced morphine-induced analgesia. Moreover, repeated administration of morphine at doses of 3 mg/kg (ip) or 5 mg/kg (ip) caused a tolerance to the morphine on the 5th or 7th day, respectively. In contrast, the combination of bLF (100 mg/kg, ip) with morphine (3 mg/kg, ip) retarded the development of tolerance to the 9th day, although bLF did not show any effect on the mice that had obtained tolerance to morphine. Furthermore, the potentiative effect of bLF was partially blocked by pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and completely blocked by 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor. Methylene blue (MB), a guanylate cyclase (GC) inhibitor, also dose-dependently prevented the potentiative effect of bLF. These results suggest that bLF selectively activates nNOS and then accelerates NO production. The increased NO in turn modulates the GC activity and finally enhances the endogenous opioid system via cyclic guanosine monophosphate production. We conclude that bLF may block the development of tolerance to morphine in mice, possibly via the selective activation of nNOS.
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PMID:Milk-derived lactoferrin may block tolerance to morphine analgesia. 1638 99

The mechanism of action underlying the "analgesic activity" of diazepam remains unclear. In this study, the possible participation of the GABA/benzodiazepine receptor and the nitric oxide-cyclic GMP (NO-cGMP) pathway was assessed utilizing the pain-induced functional impairment model in the rat (PIFIR). Nociception was induced by an intra-articular injection of 15% uric acid. Diazepam (1 and 2 mg/kg, i.p.) reversed the dysfunction induced by uric acid. Flumazenil (10 mg/kg, i.p.), a GABA/benzodiazepine receptor antagonist, abolished the "antinociceptive-like effect" of diazepam (at 2 mg/kg). The "antinociceptive-like effect" of diazepam (at 2 mg/kg) was antagonized by the non-selective nitric oxide synthase (NOS) inhibitor, Nomega-L-nitro-arginine methyl ester hydrochloride (L-NAME, 5 mg/kg, s.c.) (but not by its inactive isomer), and by the selective neuronal NOS inhibitor, 7-nitroindazole (7-NI, 1 mg/kg, i.p). While, the NO precursor, l-arginine (125 mg/kg, s.c.), but not d-arginine (125 mg/kg, s.c.), increased the "antinociceptive-like effect" of a non-effective dose of diazepam (1 mg/kg). Methylene blue (10 mg/kg, i.p.), a guanylate cyclase inhibitor, also prevented the "antinociceptive-like effect" of diazepam (at 2 mg/kg). These results suggest that the GABA/benzodiazepine receptor and the NO-cGMP pathway participate in the "antinociceptive-like effect" of diazepam.
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PMID:Participation of the GABA/benzodiazepine receptor and the NO-cyclicGMP pathway in the "antinociceptive-like effects" of diazepam. 1863 99

The aim of this research is to investigate the vasorelaxing effects and mechanisms involved in the phytoestrogen alpha-zearalanol (alpha-ZAL) in rat thoracic aortas rings. Intact or endothelium denuded rat thoracic aortas rings were put in individual organ chamber to observe the endothelium-dependent or independent vasorelaxing effects of alpha-ZAL (10(-10)-10(-5) M). The thoracic aortas rings were pre-contracted with phenylephrine. The relaxing effects of alpha-ZAL were observed and the influence of N(omega)-nitro-L-arginine methylester (L-NAME, NOS inhibitor), methylene blue (MB, guanylate cyclase inhibitor), charybdotoxin (ChTX, Ca(2+)-activated K+ channel blocker), glibenclamide (ATP-sensitive K+ channel blocker), (-) BayK8644 (L-type Ca2+ channel agonist) and ICI182,780 (estrogen receptor antagonist) were pre-incubated with alpha-ZAL, respectively, to explore the possible mechanisms involved in this vasorelaxation. Furthermore, the Phospho-eNOS expression and cGMP level in the aortas tissue were detected by Western blot and radioimmunity, respectively; the NO level in perfusate was assaied by chromatometry. Our result showed that alpha-ZAL (10(-10)-10(-5) M) induced both endothelium-dependent and -independent relaxation of rat thoracic aortas rings. The vasorelaxing effects of alpha-ZAL were dose-dependent whether the endothelium was intact or not. In endothelium-intact aortas rings, alpha-ZAL-induced vasorelaxation might be inhibited by L-NAME, MB, charybdotoxin, glibenclamide and (-) BayK8644, but not ICI182,780. (-) BayK8644 could also inhibit alpha-ZAL-induced vasorelaxation in endothelium-denuded aortas rings.10(-7)-10(-5) M alpha-ZAL might induce the Phospho-eNOS expression in thoracic aorta tissue, increase the NO level in perfusate and cGMP content in thoracic aorta tissue. Meanwhile, L-NAME might decrease both NO and its downstream cGMP level. Methylene blue might decrease the level of cGMP. These results suggest that alpha-ZAL induces a partly endothelium-dependent relaxation of rat thoracic aortas rings; the possible mechanisms involved in this rapid vasorelaxation include activation of eNOS/NO/cGMP pathway, opening of VSMCs ATP-sensitive and Ca(2+)-activated K+ channels through secretion of EDHF from endothelium. Furthermore, this relaxation also appears to be mediated by both direct and indirect inhibition of voltage-dependent Ca2+ channel of VSMCs, while it is not concerned with activation of estrogen receptor.
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PMID:Relaxing effects of phytoestrogen alpha-zearalanol on rat thoracic aorta rings in vitro. 1976 45

The aim of present study was to investigate the effect of hydroalcoholic extract of Ruta chalepensis (Rutaceae) leaves on rat ileum contractility and possible mechanism(s) involved. Ruta chalepensis extract was prepared by maceration method (ethanol 70%). Terminal portion of ileum (2 cm) was dissected out from male Wistar rats and mounted in an organ bath containing air bubbled Tyrode solution with 1 g initial tension and ileal contraction induced by KCl (60 mM) was recorded. The spasmolytic effect of the cumulative concentrations of extracts (0.01-0.07 mg mL(-1)) was reduced after tissue incubation with L-NAME (100 microM, 20 min). Methylene blue (30 microM) reduced the extracts (0.01-0.07 mg mL(-1)) spasmolytic effect (p < 0.001). Furthermore, it seems that the portion relaxatory effect of Rue extract on the rat ileum may be due to nitric oxide and the antispasmodic activity of the extract was mainly through a cGMP-dependent mechanism.
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PMID:The role of NO and cGMP in antispasmodic activity of Ruta chalepensis leaf extract on rat ileum. 2041 42

Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.
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PMID:Indole alkaloids and anti-nociceptive mechanisms of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract. 2988 85


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