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)

Epidermolysis bullosa pruriginosa is a recently recognized variant of dystrophic epidermolysis bullosa (DEB) characterized by severe pruritus and scarring, mainly involving the extensors of the extremities. In this study, we searched for mutations in the type VII collagen gene (COL7A1) using polymerase chain reaction amplification of exonic segments of COL7A1, followed by heteroduplex analysis, in a Chinese pedigree with dominant DEB displaying a striking anastomosing network of lichenoid papules and scarring. The study revealed a G-to-A transition at nucleotide 6724 within exon 85 of COL7A1, converting a glycine to an arginine (G2242R) within the triple-helical domain of the type VII collagen in affected individuals. These findings demonstrate that EB pruriginosa in this family is a clinical variant of dominant DEB.
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PMID:A glycine-to-arginine substitution in the triple-helical domain of type VII collagen in a family with dominant dystrophic epidermolysis bullosa pruriginosa. 918 28

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

It has been reported that antihistamines do not fully modify symptoms of allergic conjunctivitis in clinical settings, suggesting that histamine is not the only contributor to symptom generation in the disease. However, in the majority of experimental allergic conjunctivitis models, antihistamines are very effective in the reduction of symptoms. In the present study, we used our recently developed guinea pig model of allergic conjunctivitis and evaluated whether involvement of histamine in the induction of symptoms of allergic conjunctivitis is altered by multiple antigen challenges. Guinea pigs were sensitized by intraperitoneal injection of Japanese cedar pollen extracts adsorbed on aluminum hydroxide gel, and then challenged by dropping a pollen suspension without the adjuvant on each eye once a week until the 15th challenge. The magnitude of the conjunctivitis intensity score (CIS), itch-associated scratching response and albumin leakage were found to increase with repeated challenges. At the 1st-3rd challenges, histamine H(1) receptor antagonist, mepyramine (10 mg/kg, p.o.), strongly reduced all these symptoms. However, symptoms at the 5th-15th challenges were not inhibited by mepyramine. On the other hand, a nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (10 mg/kg, i.v.), potently inhibited the increase of CIS and albumin leakage at the 15th challenge. In conclusion, histamine involvement in the induction of conjunctivitis symptoms in our model was diminished by multiple antigen challenges. The allergic conjunctivitis at the chronic stage is partly mediated by nitric oxide (NO) derived from NOSs that may be activated by mediators other than histamine. The histamine-independent allergic conjunctivitis may be useful for analyzing mechanisms underlying chronic conjunctivitis.
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PMID:Multiple cedar pollen challenge diminishes involvement of histamine in allergic conjunctivitis of Guinea pigs. 1464 73

Anaphylaxis is a severe, life-threatening allergic reaction, affecting both children and adults. The occurrence of anaphylaxis is not as rare as generally believed (1.21% to 15.04% of the US population). Often the cause of this reaction remain unknown, mainly due to the difficulty in defining the outbreaking causes. Herein, we describe an interesting case of a patient, who developed an anaphylactic reaction after the bite of a pigeon tick. During the last 2 years, in wintertime, the patient often came to the emergency room for general rash and swelling, hypotension and tachycardia preceded by itching and general distress. Notably, the symptoms manifested themselves as night fell. In two particular occasions the patient reached the hospital in a state of shock. After another episode of general swelling, the patient was invited to examine her domestic environment. She brought us some parasites, collected at home, particularly on the bed. A morphological examination by entomologists proved these parasites to belong to Argas reflexus (Arg.r.), one of the 31 species of soft ticks. The presence of specific IgE to a protein secreted by the Arg.r. salivary glands was in favour of immediate-type systemic reaction, as supposed by the clinical history.
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PMID:Anaphylactic shock to Argas reflexus bite. 1585 66

We examined whether the proteinase-activated receptor-2 (PAR2) agonist, H-Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL-NH2), could induce scratching behavior in mice. Intradermal injections of SLIGRL-NH2 (10-50 microg) evoked dose dependent scratching. This behavior peaked near 5 min and returned to preinjection levels within 30 min. Pretreatment of animals with a histamine H1 receptor antagonist, pyrilamine, blocked histamine induced scratching, but it had little effect on SLIGRL scratching. Our study suggests that PAR2 mediates histamine independent itch.
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PMID:Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2. 1635 90

This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-886 (10 mg/kg), and the glucocorticoid betamethasone 17-valerate (3 mg/kg) inhibited the scratching. The scratching was not affected by the cyclooxygenase inhibitors indomethacin and ketoprofen, the TP prostanoid receptor antagonist SQ-29548, the leukotriene B(4) antagonist ONO-4057, the cysteinyl leukotriene antagonist pranlucast, the leukotriene D(4) antagonist MK-571, the platelet-activating factor antagonist CV-3988, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester, the H(2) histamine-receptor antagonist cimetidine, the H(1) histamine-receptor antagonist terfenadine plus cimetidine, and cypoheptadine that blocks the 5-HT(1/2) serotonin receptors. Zileuton (100 mg/kg) inhibited the increased activity of the cutaneous nerve branch induced by an intradermal injection of the extract, suggesting the peripheral action. Zileuton and MK-886 (10 and 100 microM) did not affect high K(+)-induced increase in intracellular Ca(2+) concentration in cultured dorsal root ganglion neurons. The results suggest that 5-lipoxygenase metabolite(s) other than leukotriene B(4) and cysteinyl leukotrienes are involved in mosquito allergy-associated itching.
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PMID:Possible involvement of 5-lipoxygenase metabolite in itch-associated response of mosquito allergy in mice. 1782 70

The uremic pruritus is a very painful symptom suffered by chronic haemodialysis patients and is observed in 22 to 74% of the subjects. The causes of uremic pruritus have not yet been clarified. During the last 20 to 30 years it has been focused on altogether 5 different pathophysiological hypotheses: stimulating influences (e.g. calcium phosphate deposits in the epidermis), stimuli (e.g. secondary hyperparathyroidism), neuropathic injuries (e.g. disturbance of the cutaneous innervation in patients with uremic peripheral neuropathy), and central nervous changes (e.g. accumulation of endorphins in uremic patients which is associated with increasing pruritus), and immunologic conditions. The last mentioned immunological hypothesis has increasing importance, not at least based on the fact that the application of a topical calcineurin inhibitor (tacrolimus) improves the uremic pruritus. However, this fact could not be confirmed in a recent prospective placebo-controlled study from the USA. Only after kidney transplantation with a functioning transplant the uremic pruritus is stopped. That is why no causal therapy exists so far. Actually, the uremic pruritus has to be treated by topical and systemic means in a symptomatic and polypragmatic way only. Urea represents one of the most important "natural moisturizing factors" which are responsible for the hydration of the skin. It has been demonstrated that older patients have decreased urea levels within the stratum corneum of the epidermis, whereas in patients with terminal kidney insufficiency - despite dryness of the skin - as a paradox finding elevated levels of urea have been assessed in the stratum corneum. Because of this reason, the meaning of urea as part of the "natural moisturizing factors" system is not understood, until now. However, there are very promising results of clinical phase II studies showing a significant effect of topical application of 2.5% L-arginine hydrochlorid ointment - a semi-essential amino acid - on improvement of dryness and, in particular, on improvement of pruritus in haemodialysis patients.
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PMID:[Pruritus and dryness of the skin in chronic kidney insufficiency and dialysis patients - a review]. 1965 38

Chemical modifications of nociceptin/orphanin FQ (N/OFQ) peptide that result in increased potency and resistance to degradation have recently lead to the discovery of [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112), a novel N/OFQ peptide (NOP) receptor agonist. The aim of this study was to investigate the pharmacological profile of intrathecally administered UFP-112 in monkeys under different behavioral assays. Intrathecal UFP-112 (1-10 nmol) dose-dependently produced antinociception against an acute noxious stimulus (50 degrees C water) and capsaicin-induced thermal hyperalgesia. Intrathecal UFP-112-induced antinociception could be reversed by a NOP receptor antagonist, J-113397 (0.1mg/kg), but not by a classic opioid receptor antagonist, naltrexone (0.03 mg/kg). Like intrathecal morphine, UFP-112 produced antinociception in two primate pain models with a similar magnitude of effectiveness and a similar duration of action that last for 4-5h. Unlike intrathecal morphine, UFP-112 did not produce itch/scratching responses. In addition, intrathecal inactive doses of UFP-112 and morphine produced significant antinociceptive effects when given in combination without increasing scratching responses. These results demonstrated that intrathecal UFP-112 produced long-lasting morphine-comparable antinociceptive effects without potential itch side effect. This study is the first to provide functional evidence that selective NOP receptor agonists such as UFP-112 alone or in conjunction with morphine may improve the quality of spinal analgesia.
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PMID:Long-lasting antinociceptive spinal effects in primates of the novel nociceptin/orphanin FQ receptor agonist UFP-112. 1994 94

Itch has been defined as an unpleasant skin sensation that triggers the urge to scratch. Primary sensory dorsal root ganglia neurons detect itch stimuli through peripheral axons in the skin, playing an important role in generating itch. Itch is broadly categorized as histaminergic (sensitive to antihistamines) or nonhistaminergic. The peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) is an itch-inducing agent widely used to study histamine-independent itch. Here, we show that Mrgprs (Mas-related G protein-coupled receptors), particularly MrgprC11, rather than PAR2 (protease-activated receptor 2) as previously thought, mediate this type of itch. A shorter peptide, SLIGR, which specifically activates PAR2 but not MrgprC11, induced thermal pain hypersensitivity in mice but not a scratch response. Therefore, although both Mrgpr and PAR2 are SLIGRL-responsive G protein-coupled receptors present in dorsal root ganglia, each plays a specific role in mediating itch and pain.
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PMID:The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia. 2177 81


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