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)

The effects of peptidase inhibitors were examined upon behavioural responses including scratch, bite and lick produced by intrathecal (IT) injection of substance P (SP) and neurokinin A (NK A) in mice. Phosphoramidon (0.002-2.0 nmol), an endopeptidase-24.11 inhibitor, simultaneously injected with SP or NK A, remarkably enhanced and prolonged SP- or NK A-induced behavioural response in a dose-dependent manner. The behavioural response to SP was significantly increased by 2.0 nmol of bestatin, an aminopeptidase inhibitor, but not by 1.0 nmol. Captopril, an angiotensin-converting enzyme inhibitor, was without effect on both tachykinin-induced responses. When phosphoramidon was injected together with bestatin and captopril which have no significant effect alone, SP- or NK A-induced behavioral response was significantly increased. These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level.
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PMID:Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice. 170 5

This report describes the influence of bombesin on the gross behavior of goldfish, frogs, mice, rats, guinea pigs, rabbits, chicks, pigeons and monkeys. Goldfish, frogs, chicks and pigeons were overtly unaffected by bombesin given centrally and/or peripherally. Mice, rats, guinea pigs, rabbits and monkeys responded quickly to intracerebroventricular (i.c.v.) and/or intrathecal (i.th.) administration of bombesin by displaying a range of behaviors suggestive of altered skin sensation. In mice, bombesin was essentially equipotent as a scratch inducer by i.c.v. and i.th. routes (A50 = 0.010-0.019 microgram) but 6800 times less potent i.p. In rats, bombesin-induced grooming and scratching behaviors were shown to be qualitatively different from those associated with ACTH-(1-24) and thyrotropin releasing hormone. Spantide and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P (both at 0.20, 0.50 and 0.80 microgram i.c.v.), two proposed bombesin receptor antagonists, did not markedly influence bombesin-induced scratching or hypothermia in rats.
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PMID:Effects of bombesin on behavior. 240 26

Substance P (SP) injected into intraspinal (i.s.) spaces caused mice to vigorously scratch and bite their skins in an apparent reaction to a perceived cutaneous sensation. The scratching behavior was similar to the reciprocal hindlimb-scratching syndrome (RHS) described for intracranial (i.c.) SP injections. Radiotracer experiments, as well as potency and latency measurements, demonstrated that SP-induced scratching, whether induced by the i.c. or i.s. route, was due to SP receptor stimulation in the cervicothoracic cord. Similarly, biting was due to SP stimulation of the lumbosacral spinal cord. Mice coated with capsaicin, an irritant chemical, scratched and bit the coated areas in a manner similar to animals injected with i.s. SP. Standard analgesics depressed this scratching behavior elicited by topical capsaicin. Non-analgesic drugs, with the exception of amphetamine, did not affect capsaicin-induced pain. It is concluded that i.s. SP induces a painful sensory experience. Some piperazinone derivatives of substance P's C-terminal hexapeptide are shown to specifically antagonize the scratching induced by i.s. SP with little or no effect on motor behavior. These antagonists depressed scratching elicited by topical capsaicin and were analgesic on the hot-plate test. It is concluded that SP is a natural neurotransmitter for pain and that antagonism of endogenous SP systems causes analgesia.
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PMID:Analgesic activities of spinal cord substance P antagonists implicate substance P as a neurotransmitter of pain sensation. 242 37

The purpose of this study was to monitor histamine release in immediate-type hypersensitivity reactions in the skin of 10 atopic patients, sensitive to cow, by using the microdialysis technique. Three healthy subjects, without any atopic features or background, served as the control group. The probe inserted into the forearm dermal skin was perfused with isotonic saline solution. Samples were collected at 15-min intervals. After the first allergen challenge of four prick tests close to the probe with cow allergen extract, the skin was similarly repricked again in five patients and three healthy subjects, and in five other patients, 25 microliters of 10 mumol/l substance P (SP) was injected intracutaneously. The samples were analysed for histamine by radioenzyme assay. The patients were clinically evaluated for allergic symptoms, prick- and scratch-patch test reactivity and for serum cow-specific, and total, IgE levels. The baseline histamine concentration was 7.5 +/- 4.0 nmol/l (mean +/- standard deviation: SD; n = 10). After the allergen challenge, the histamine concentration in the consecutive samples was 11.9 +/- 11.0 nmol/l, 91.1 +/- 127.3 nmol/l, 61.0 +/- 94.2 nmol/l and 33.7 +/- 53.7 nmol/l. The peak concentration was detected in the 15-30 min fraction, and it varied between 0 and 406 nmol/l regardless of the weal size. The second allergen challenge was unable to induce marked additional histamine release, but SP induced extensive histamine liberation in those patients who did not exhibit histamine release during the preceding prick tests. In three healthy subjects, the baseline histamine concentration was 6.2 +/- 3.9 nmol/l. After the allergen challenge, no additional histamine liberation could be measured. Surprisingly, the histamine release was not related to the size of the cow-induced weal nor was it related to any specific allergic symptoms or IgE levels. The results suggest that, in some patients, mast cell mediators other than histamine play a significant part in immediate-type allergic reactions of skin.
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PMID:Histamine release in skin monitored with the microdialysis technique does not correlate with the weal size induced by cow allergen. 874 92

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)
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PMID:Recent studies of cutaneous nociception in atopic and non-atopic subjects. 1009 77

In a search for new anti-pruritic drugs we screened methanol extracts of 33 herbal medicines which have been used for cutaneous diseases for their antipruritic activity using substance P (SP) as a pruritogen in mice. When administered perorally 30 min before SP injection, methanol extracts of 6 of these herbal medicines, the root of Scrophularia ningpoensis Hemsl., the root of Patrinia villosa (Thunb.) Juss, the fruit of Forsythia suspenna Vahl, the rhizome of Cimicifuga dahurica (Turcz.) Maxim., the aerial part of Schizonepeta tenuifolia Briq. and the fruit of Cnidium monnieri (L.) Cuss, inhibited SP-induced itch-scratch response at a dose of 200 mg/kg with-out affecting locomotor activity. Dose dependence of these 6 extracts (50-500 mg/kg) was investigated and all of them inhibited SP-induced itch-scratch response, with extracts from Scrophularia ningpoensis, Schizonepeta tenuifolia and Cnidium monnieri showing particularly significant inhibition. The results suggest that these 6 methanol extracts have inhibitory activity against SP-induced itching.
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PMID:Inhibitory effects of methanol extracts of herbal medicines on substance P-induced itch-scratch response. 1082 72

Anti-scratch effects of oxatomide and epinastine were examined in mice. Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and substance P injection, respectively. Although oxatomide and epinastine failed to inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction significantly. The drugs potently inhibited both scratching behavior and cutaneous reaction in ICR mice. They also inhibited scratching behavior and cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to affect them. Histamine did not induce frequent scratching behavior in BALB/c and ddY mice. These results indicate that oxatomide and epinastine inhibit the scratching behavior in ICR mice associated with passive cutaneous anaphylaxis mainly through an antagonistic action on histamine H(1) receptors. The results also indicate that these drugs inhibit substance P-induced scratching behavior in ddY mice through an action independent of the antagonistic action on histamine H(1) receptors.
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PMID:Evaluation of anti-scratch properties of oxatomide and epinastine in mice. 1091 87

To clarify the behavioral and pathological features of spontaneous scratching of NC mice with mite-induced chronic dermatitis, we investigated the spontaneous and pruritogen-evoked scratching of NC mice. Although the frequency of scratching of NC mouse did not increase under specific pathogen-free environment, it gradually and markedly increased from 3 to 6 weeks after transfer to conventional environment. The onset of increase in spontaneous scratching was similar to that of dermatitis development and the elevation of plasma concentration of immunoglobulin E. At chronic stage (16 weeks after environment change), the frequency of spontaneous scratching was roughly parallel to the degree of dermatitis, but not to the plasma concentration of immunoglobulin E. The spontaneous scratching of NC mice with dermatitis was inhibited by distraction and the opioid antagonist naltrexone, suggesting that the scratching is itch-associated response. An intradermal injection of serotonin, but not histamine and substance P, elicited scratching of the injected site. Methysergide and cyproheptadine inhibited the serotonin-induced scratching but not spontaneous scratching. The results suggest that marked elevation of plasma immunoglobulin E is not always the cause of spontaneous itch-associated response of NC mice with dermatitis. Serotonin, histamine and substance P may not play an important role in spontaneous itch-scratch response at a chronic stage.
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PMID:Characterization of itch-associated responses of NC mice with mite-induced chronic dermatitis. 1115 60

Intradermal injection of substance P elicits an itch sensation in human subjects and an itch-associated response in mice. The substance P-induced itch-associated response in mice is not inhibited by antihistamine. Therefore, the mechanisms of substance P-induced itch-associated response are unclear. In this study, we demonstrated one of the mechanisms. Substance P induces an arachidonate cascade to produce prostaglandins and leukotriene. In this study we considered whether arachidonate metabolites are involved in the substance P-induced itch-associated response. A phospholipase A(2) inhibitor arachidoryltrifluoromethyl ketone inhibited the substance P-induced itch-associated response in mice. Pre treatment with the glucocorticoids betamethasone and dexamethasone also produced inhibition of the substance P-induced itch-associated response in mice as well as humans. The 5-lipoxygenase inhibitor zileuton, but not the cyclooxygenase inhibitors indomethacin and diclofenac, suppressed substance P-induced itch-associated response. The leukotriene B(4) receptor antagonist 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-5E-hexenyl]oxyphenoxy]valeric acid produced inhibition, whereas pranlukast (leukotriene C(4)/D(4)/E(4) receptor antagonist) and 5(Z)-7-[1S,2S, 3S,5R-3-(trans-b-styren)sulfonamido-6,6-dimethylbi cyclo(3,1,1)hept-2-yl]-5-heptenoic acid (EP(1) receptor antagonist) were without effect. Furthermore, when the production of leukotriene B(4) and prostaglandin E(2) was measured in skin injected with substance P and in mouse keratinocytes applied with substance P, the level of both products increased. As leukotriene B(4), but not prostaglandin E(2), also induces the itch-associated response in mice, these results suggest that leukotriene B(4) and keratinocytes, cutaneous cells which produced leukotriene B(4), play an important role in substance P-induced itch-scratch response in mice. Leukotriene B(4) receptor antagonist and 5-lipoxygenase inhibitor may be novel antipruritic drugs.
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PMID:Involvement of leukotriene B(4) in substance P-induced itch-associated response in mice. 1188 31

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.
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PMID:The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice. 1625 75


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