Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In atopic dermatitis patients, pruritus is a severe symptom that is difficult to treat. It is previously reported that TRK-820, a kappa-opioid receptor agonist, reduces murine scratching behavior induced by an intradermal injection of histamine or substance P or an intracisternal injection of morphine. It is also reported that TRK-820 ameliorates the intractable pruritus in hemodialysis patients. However, it is still unclear whether TRK-820 possesses antipruritic effects on the pruritus in dermatitis patients. Therefore, the effect of TRK-820 on scratching behavior in NC/Nga mice maintained in a conventional environment, an animal model of atopic dermatitis, was examined. Oral TRK-820 (10-100 microg/kg) inhibited the scratching behavior but did not affect the locomotor activity. On the other hand, ketotifen (3-30 mg/kg, po), an antihistamine, did not attenuate the scratching behavior. TRK-820 showed the highest selectivity and activity for kappa-opioid receptor among all human opioid receptors. Release of various inflammatory mediators from a variety of cells and activity of nitric oxide synthase were not altered by TRK-820. This compound showed much lower affinities for other receptors than that for opioid receptors. These results suggest that TRK-820 is effective against antihistamine-resistant pruritus in atopic dermatitis patients via the kappa opioid receptor.
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PMID:[Effect of TRK-820, a selective kappa opioid receptor agonist, on scratching behavior in an animal model of atopic dermatitis]. 1851 86

Uremic pruritus is a common and sometimes severe complication of chronic renal failure. Itch affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis and 25% of patients with preterminal chronic renal failure. The mechanism underlying uremic pruritus is poorly understood; possibilities include histamin, proteases, interleukin-2 and TNF- produced by skin mast-cells, substance P, neuropathy and neurological changes, high level of Ca, P, PTH, Al, Mg, divalent ion abnormalities, hypervitaminosis A, inflammation, or some combination of these. Therapeutic measures include regular efficient dialysis, transplantation, topical measures as an emollients, topical steroids, systemic measures as diet, opioids and physical treatment with phototherapy, acupuncture etc. Treatment results are highly variable and more research is needed to understand the patophysiology of this condition and to establish more reliable treatments. Most effective treatments in this moment are efficient dialysis, dietary restrictions, phosphate-binding therapy and phototherapy.
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PMID:[Uremic pruritus]. 1857 30

There are numerous studies of the pruritus-producing effects of histamine, serotonin, tryptase, substance P and interleukin-2 in humans and mice, but very little reported in dogs even though a common reason dogs are presented to veterinarians is pruritus. The aim of this study was to determine whether substances known to cause pruritus in humans also cause pruritus in dogs. Twenty-five clinically healthy research beagle dogs were included in the study. All dogs first received an intradermal injection of 0.05 mL saline as a control substance and were video-recorded for 20 min before and after the injection. Twenty-four hours later the dogs were randomly divided into five groups of five dogs each and randomly assigned to receive histamine, serotonin, tryptase, substance P or interleukin-2 injected intradermally each at the volume of 0.05 mL. On subsequent days, increasing concentrations of each substance were used. Before (baseline) and after the injection of each concentration of the substances, the dogs were video-recorded for 20 min. The frequency and character of pruritus episodes (scratching, licking, chewing, rubbing or rolling) were noted and these data were used for statistical analysis. The number of pruritus episodes was compared among baseline, saline and the different concentrations of each substance. The results showed that dogs did not have a significant increase in pruritic behaviour above baseline or saline after injection of any of the investigated substances (generalized linear model; P = 0.23).
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PMID:Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin-2 in healthy dogs. 1915 12

Itching and sneezing represent two of the main bothersome symptoms, apart from nasal obstruction and rhinorrhea in allergic rhinitis. Apparently, activation of the central and peripheral nervous system plays a major role in the pathophysiology of this process. Sensory nerves of the afferent trigeminal system including myelinated Adelta-fibres and thin, non-myelinated C-fibres of the nasal mucosa transmit signals generating sensations, including itching and motor reflexes, such as sneezing. These nerves can be stimulated by products of allergic reactions and by external physical and chemical irritants. Via axon reflex inflammatory neuropeptides including the tachykinins substance P (SP) and neurokinin A (NKA) and the calcitonin gene related peptide are released, leading to vasodilatation, increased vascular permeability (concept of "neurogenic inflammation"), glandular activation, leukocyte recruitment and differentiation of immune cells including mast cells, eosinophils, lymphocytes and macrophages. The present paper describes nasal (micro-) anatomy and innervation and explains the central and peripheral mechanisms initiating itching and sneezing in allergic rhinitis. Further, the role of neuropeptides and neurotrophins with regard to neuronal and immune cell activation which might play a key role in the future treatment of allergic rhinitis are discussed.
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PMID:Pathophysiology of itching and sneezing in allergic rhinitis. 1916 1

Atopic dermatitis (AD) is a common chronic or chronically relapsing, severely pruritic, eczematous skin disease. Recently, substance P (SP) has been demonstrated to be one of the important neuropeptides for mediating itch-scratch and stress-scratch cycles. In this study, we examined the severity scores, itch scores and plasma SP levels in 19 patients with AD treated with standard topical therapy with or without an oral antihistamine, olopatadine hydrochloride, for 4 weeks. The standard therapy decreased SCORAD scores, itch behavioral rating scores and plasma SP levels at post-treatment in the mass, but the topical therapy with olopatadine was more effective than the topical therapy alone, suggesting a potential additive effect.
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PMID:Severity scores, itch scores and plasma substance P levels in atopic dermatitis treated with standard topical therapy with oral olopatadine hydrochloride. 1934 55

In the past it was widely believed that pain and itching are transmitted by the same nerve pathway with the low intensity stimulation of unmyelinated polymodal C fibers resulting in sensation of pruritus whereas high intensity stimulation causing pain. In recent experiments however, stimulation of single unmyelinated C fibers led to the identification of two kinds of fibers. Stimulation of most of these fibers induces pain, whereas a small number of fibers provoke the sensation of itching. Pruritus is an unpleasant sensation, often accompanied by scratching. It may present due to a number of cutaneous diseases or internal disorders. Pruritus may be caused by some chemical substances as histamine, prostaglandins, proteases and substance P. This review describes the existence of pruritus in different internal disorders. It is quite important the reason of pruritus to be discovered, for the application of an adequate therapy.
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PMID:Pruritus in certain internal diseases. 1958 80

Many medicines exist which can cause pruritus (itching) as "serious adverse events." Many severe pruritic conditions respond poorly to histamine H1 receptor antagonists; there is no generally accepted antipruritic treatment. Recently described histamine H4 receptors are expressed in haematopoietic cells and have been linked to the pathology of allergy and asthma. We previously reported their expression in human dermal fibroblasts; in this study we have investigated H4 receptor expression in human epidermal tissue and found it to be greater in keratinocytes in the epidermal upper layer than in the lower layer. We have also investigated the effect of histamine H4 receptor antagonists on histamine H1 receptor antagonist-resistant pruritus using a mouse model. Scratching behavior was induced by histamine (300 nmol) or substance P (100 nmol) injected intradermally into the rostral part of the back of each mouse. Fexofenadine, a histamine H1 receptor antagonist, reduced scratching induced by histamine but not by substance P, whereas JNJ7777120, a histamine H4 receptor antagonist, significantly reduced both histamine- and substance P-induced scratching. These results suggest that H4 receptor antagonists may be useful for treatment of H1 receptor antagonist-resistant pruritus.
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PMID:Expression of histamine H4 receptor in human epidermal tissues and attenuation of experimental pruritus using H4 receptor antagonist. 1965 66

Itching is the most important problem in atopic dermatitis and tacrolimus has been suggested to attenuate the itching by topical application. However, the anti-itch mechanism of tacrolimus has not been well elucidated. In the present study, an allergic dermatitis accompanied by frequent scratching behaviors was induced by repeated paintings with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse ear and the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior were comparatively examined. Repeated DNFB paintings caused a typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behaviors. Both tacrolimus and dexamethasone given topically for 10 days before the final challenge significantly inhibited the ear swelling and reduced the expression of interferon-gamma mRNA. Dexamethasone inhibited the accumulation of eosinophils completely, although tacrolimus did not. Both drugs did not affect the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior, whereas dexamethasone failed to affect it. Repeated DNFB challenge depleted substance P in the dermis. Treatment with tacrolimus before the final challenge completely inhibited the recovery of substance P content, whereas dexamethasone facilitated the recovery. DNFB-induced ear swelling and scratching behavior were significantly inhibited by FK888, a tachykinin NK(1) receptor antagonist. Therefore, substance P seems to participate in the induction of ear swelling and scratching behavior upon final challenge with DNFB, and depletion of substance P by tacrolimus in the dermis contributes to its inhibition of ear swelling and scratching behavior at least in part.
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PMID:Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus. 1981 45

The itch-scratch cycle aggravates chronic inflammatory skin diseases. We have previously reported that mice begin to scratch themselves within several minutes after skin-scratching stimulation. This is associated with an increase in release of substance P (SP) from sensory nerve fibers in the skin, and the self-scratching behavior is suppressed by neurokinin-1 receptor (NK-1R) antagonist. Thus, SP may play a pivotal role in self-scratching behavior. The purpose of this study was to investigate the effect of second-generation histamine H(1)-receptor antagonists on self-scratching behavior in mice. After oral administration of epinastine hydrochloride (epinastine) (total dose 50 +/- 5 mg/kg for 7 days) or the vehicle only to ICR mice for 7 days, skin-scratching stimulation was administered to the dorsal skin for 10 min. Self-scratching behavior was recorded by video camera for 10 min. Twenty-four hours later, skin tissue was harvested and stained with toluidine blue. Immunohistochemical staining for SP was performed, and SP and nerve growth factor (NGF) concentrations were measured by enzyme-linked immunosorbent assay. Self-scratching behavior, mast cell degranulation, and NGF concentration decreased, and the length of SP-positive nerve fibers and SP concentrations increased significantly in the epinastine-treated group, when compared with the vehicle control group. We conclude that epinastine inhibits mast cell degranulation by attenuating SP release from sensory nerve fibers, which results in inhibition of self-scratching behavior. These results suggest that second-generation histamine H(1)-receptor antagonists might efficaciously control itch-scratch cycle-related skin diseases.
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PMID:Effect of epinastine hydrochloride on murine self-scratching behavior after skin-scratching stimulation. 1993 55

Itch is thought to be signaled by pruritogen-responsive neurons in the superficial spinal dorsal horn. Many neurons here express the substance P NK-1 receptor. We investigated whether neurotoxic destruction of spinal NK-1-expressing neurons affected itch-related scratching behavior. Rats received intracisternal substance P conjugated to saporin (SP-SAP), or saporin (SAP) only (controls), and were subsequently tested for scratching behavior elicited by intradermal 5-hydroxytryptamine. SAP controls exhibited dose-related hindlimb scratching, which was significantly attenuated in SP-SAP-treated rats. There was a virtual absence of NK-1 immunoreactive neurons in superficial laminae of the upper cervical and medullary dorsal horn in SP-SAP-treated rats. These results indicate that superficial dorsal horn neurons expressing NK-1 receptors play a key role in spinal itch transmission.
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PMID:Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. 2012 52


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