Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NC mice, a model for atopic dermatitis, showed scratching behavior when kept under conventional environment. The scratching behavior of NC mice was suppressed by distraction or by the administration of naltrexone (1 mg/kg, s.c.), an opioid antagonist. These results suggest that such scratching behavior is itch-associated response. The itch-associated response of the NC mice was significantly suppressed by an intravenous injection of nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), but not D-NAME (10 mg/kg) and saline. Intracutaneous NO production in the rostral back, a region which the NC mice mainly scratched, was markedly increased as compared with the caudal back, a non-scratched region. The increased NO production in the rostral back of NC mice was decreased by the intravenous injection of L-NAME (10 mg/kg). These results suggest that NO and NO synthase are new target in the treatment of atopic pruritus.
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PMID:[Involvement of nitric oxide in itch-scratch response of NC mice]. 1062 49

1 Substance P (SP) elicits itch and itch-associated responses in humans and mice, respectively. In mice, NK(1) tachykinin receptors are involved in SP-induced itch-associated responses, scratching, and mast cells do not play a critical role. The present study was conducted to elucidate the role of nitric oxide (NO) on SP-induced scratching in mice. 2 An intradermal injection of SP (100 nmol site(-1)) elicited scratching in mice, and it was suppressed by an intravenous injection of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), but not by its inactive enantiomer D-NAME. Intradermal injections of L-NAME (100 nmol site(-1)), another NOS inhibitor 7-nitroindazole (10 nmol site(-1)) and the NO scavenger haemoglobin (0.01-10 nmol site(-1)) also inhibited SP-induced scratching. 3 L-NAME (100 nmol site(-1)) did not affect scratching induced by an intradermal injection of 5-hydroxytryptamine (100 nmol site(-1)). 4 Intradermal injections of L-arginine (300 nmol site(-1)) and the NO donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3; 100 nmol site(-1)) increased scratching induced by SP. Intradermal injections of L-arginine (1-1000 nmol site(-1)) or NOR3 (1-100 nmol site(-1)) alone were without effects on scratching. 5 Intradermal injections of SP (10-100 nmol site(-1)) increased the intradermal concentration of NO in a dose-dependent manner in mice. An increase in NO levels induced by SP was inhibited by L-NAME and the NK(1) tachykinin receptor antagonist L-668,169, but not by the NK(2) tachykinin receptor antagonist L-659,877. 6 SP (1-10 micro M) elicited NO production in cultured human keratinocytes and the SP-induced NO production was inhibited by L-NAME and L-668,169. 7 We conclude that intradermal SP increases NO in the skin, possibly through the action on NK(1) tachykinin receptors on the epidermal keratinocytes and that NO enhances SP-induced itch-associated responses.
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PMID:Nitric oxide enhances substance P-induced itch-associated responses in mice. 1252 91

Intradermal administration of chloroquine (CQ) provokes scratching behavior in mice. Chloroquine-induced itch is histamine-independent and we have reported that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway is involved in CQ-induced scratching behavior in mice. Previous studies have demonstrated that activation of N-methyl-d-aspartate receptors (NMDARs) induces NO production. Here we show that NMDAR antagonists significantly decrease CQ-induced scratching in mice while a non-effective dose of an NMDAR agonist potentiates the scratching behavior provoked by sub-effective doses of CQ. In contrast, combined pre-treatment with sub-effective doses of an NMDAR antagonist, MK-801, and the NO synthase inhibitor, L-N-nitro arginine methyl ester (L-NAME), decreases CQ-induced scrat-ching behavior. While intradermal administration of CQ significantly increases the concentration of intradermal nitrite, the end product of NO metabolism, effective doses of intraperitoneal and intradermal MK-801 significantly decrease intradermal nitrite levels. Likewise, administration of an effective dose of L-NAME significantly decreases CQ-induced nitrite production. We conclude that the NMDA/NO pathway in the skin modulates CQ-induced scratching behavior.
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PMID:Peripheral NMDA Receptor/NO System Blockage Inhibits Itch Responses Induced by Chloroquine in Mice. 2811 97

Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/cyclic guanosine monophosphate pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity. Thus, we aimed to investigate the effect of sumatriptan on CQ-induced scratching. We used the rostral back model of itch. Chloroquine was injected intradermally into the rostral back of NMRI mice, and the scratching behavior was evaluated by measuring the number of bouts over 30 min. We evaluated the effect of sumatriptan and combination of sumatriptan and a non-selective NO synthase inhibitor, L-N-nitro arginine methyl ester (L-NAME), on the scratching behavior. Additionally, the changes of skin, hippocampus, and cortical nitrite level after different treatments were studied. Intraperitoneal and intradermal sumatriptan attenuates CQ-induced itch which reversed by GR-127935, the selective 5-HTR1b and 5-HTR1d antagonist. Co-administration of subeffective doses of sumatriptan and L-NAME significantly decreases the scratching behavior. Intradermal injection of CQ significantly increases the intradermal nitrite levels while it does not have any significant effects on hippocampal or cortical nitrite concentrations. Likewise, the effective doses of intraperitoneal and intradermal sumatriptan significantly reduce intradermal nitrite levels. We concluded that sumatriptan suppresses CQ-induced itch most likely by activating 5-HT1b/1d receptors. This effect probably mediates through NO pathway.
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PMID:Pharmacological evidence of involvement of nitric oxide pathway in anti-pruritic effects of sumatriptan in chloroquine-induced scratching in mice. 2881 20