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)

Intradermal injection of synthetic substance P (10(-7)--10(-5) M in humans produced flare, wheal and itching. These responses were inhibited by oral pretreatment of the subjects with an antihistaminic drug (chlorcyclizine) or by local pretreatment with Compound 48/80 administered to deplete the local stores of mast-cell bound histamine. The findings indicate that the responses induced by substance P were mainly mediated by histamine released from the dermal mast cells. In contrast to previously studied histamine liberators, substance P was less potent when acting on rat mast cells in vitro than on human skin mast cells in vivo. When incubated with rat peritoneal mast cells, about 100 times higher concentrations (10(-5) M) were required to induce histamine release than in the in vivo studies on humans. It was concluded that substance P is a potent histamine liberator in human skin.
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PMID:Flare and itch induced by substance P in human skin. 8 Dec 43

The skin vascular responses (weal, flare, blood flow measurements) elicited by intradermal administration by pricking of histamine (HS) and substance P (SP) were evaluated 6 h after a single intake of anti-H1 agents displaying different activity profile on skin tests at currently recommended dosages (loratadine 10 mg, cetirizine 10 mg) as compared to placebo (P). The weal and flare response and the increases of blood flow occurring in the usual flare area after HS and SP were almost completely abolished by cetirizine. Inhibition of HS- and SP-induced weal and flare reactions was less marked after loratadine and blood flow in the expanding flare after HS and SP showed significant fluctuations over time. In view of the present results and of data obtained in previous experiments with intradermal injection of agonists, we hypothesize that mode of administration of agonists significantly influences the size of the residual weal after anti-H1 agents. We demonstrate that SP weals induced by pricking are largely inhibited by a potent H1 blockade which supports the view that this phenomenon, as well as the SP-flare, is due to SP-induced histamine liberation. We also, for the first time, report on fluctuations recorded at the edge of the developing flare with laser Doppler flowmetry early after prick testing with a weak H1 blockade. This opens up new avenues in dynamically testing H1-receptor occupancy in vivo and in situ in human skin.
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PMID:Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substance P. 128 98

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.
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PMID:Cutaneous responses to vasoactive intestinal polypeptide in chronic idiopathic urticaria. 137 Feb 36

The actions and interactions of putative mediators of inflammation, such as substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in human skin. In addition, the effects of capsaicin were examined as it is known to release (and to deplete) SP and calcitonin gene-related peptide from C-fibres. The flare evoked by bradykinin was abolished by pretreatment with lignocaine (local anesthetic), compound 48/80 (mast-cell histamine liberator), mepyramine (H1-receptor antagonist) and indomethacin (cyclo-oxygenase inhibitor) but was unaffected by atropine and ketanserin (serotonin antagonist). The weal response was not reduced by any of the drugs. The flare evoked by capsaicin was abolished by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine, atropine and ketanserin. The weal response was reduced by indomethacin. The flare response to bradykinin seems to reflect the activation of C-fibres and associated mast cells, while the flare response to capsaicin seems to reflect the activation of C-fibres only. Repeated injections of capsaicin and bradykinin produced tachyphylaxis (and cross-tachyphylaxis) and greatly reduced the SP-evoked flare. Capsaicin produced tachyphylaxis also after treatment of the skin with a local anaesthetic, suggesting that it develops independently of C-fibre impulse flow. The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the depletion of messenger peptides from the C-fibres. The flare response to SP following capsaicin- or bradykinin-induced desensitization gradually returned to normal after 5-8 weeks. The erythema evoked by PGE2 was reduced by 30% following pretreatment with lignocaine, mepyramine or compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin. 137 95

Substance P is a neuropeptide (contained in/and released from the A delta and C nerve fibers of the skin), which provokes erythema, edema, and pruritus after intradermal injection. Local pretreatment with capsaicin produces decreased substance P-dependent erythema, with edema similar to that observed before pretreatment with capsaicin. We injected histamine and in a parallel experiment, substance P in five volunteers before and after local treatment with capsaicin, with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema centered by a wheal. After treatment with 48/80, SP provoked increased erythema and a wheal. After hydroxyzine treatment, the injection of histamine produced no erythema or edema in four of the five subjects, while SP provoked erythema in all five subjects and edema similar to that observed before treatment with hydroxyzine. These data support the hypothesis that substance P provokes erythema and edema both with histamine-dependent and histamine-independent pathways.
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PMID:Substance P provokes cutaneous erythema and edema through a histamine-independent pathway. 137 8

We determined the effect of an inhibitor of neutral endopeptidase, acetorphan, on the skin responses to substance P and on the bronchostrictor effects of sodium metabisulphite aerosol in asthmatic subjects. One hour following ingestion of acetorphan (200 mg) or placebo tablets, cutaneous responses to substance P were performed in four subjects. In seven subjects, bronchial challenge with increasing concentrations of sodium metabisulphite solutions was performed and the concentration required to cause a 20% fall in baseline FEV1 determined (PC20). On the acetorphan day, there was a significant increase in the wheal and flare responses to substance P and to the diluent (0.9% NaCl) alone. However, there was no significant effect of acetorphan on the PC20 metabisulphite. We conclude that metabisulphite airway challenge in vivo may not invoke the release of endogenous neuropeptides. However, the degree of inhibition of neuropeptide breakdown by the oral dose of acetorphan used may not have been optimal.
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PMID:Effect of neutral endopeptidase inhibitor on airway function and bronchial responsiveness in asthmatic subjects. 137 94

The flare and weal reactions to intradermal injections of histamine and the peptide substance P were measured in a group of patients with atopic dermatitis and compared to reactions in a non-atopic control group. There was no significant difference in the flare areas between the controls and atopics with either reagent. The weal volumes after injection of substance P and histamine were significantly larger in the atopic group. As substance P causes mast cell histamine release, the increased weal volumes produced by substance P in the atopics may be entirely due to the exaggerated atopic weal reaction to histamine.
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PMID:Cutaneous reactions to substance P and histamine in atopic dermatitis. 169 Oct 13

Histamine H1-antagonists inhibit the weal-and-flare responses to the intradermal injection of platelet activating factor (PAF) in humans, and PAF response is reduced in histamine-depleted skin sites. This indicates that mast cell histamine release is likely to be the mechanism of this response. We have therefore studied the interaction of PAF with cutaneous mast cells by observing whether it releases histamine directly from human dispersed foreskin mast cells, potentiates the activity of known mast cell stimulants or liberates histamine releasing factors (HRFs) from human platelets and leucocytes to release mast cell histamine by an indirect mechanism. At a concentration of 100 microM both PAF C18 and PAF C16 caused near maximal release (83.5 +/- 4.3% and 88.2 +/- 4.5% respectively) of the total histamine content of the cell. This release was not inhibited in the absence of extracellular Ca2+, by the lack of metabolic energy or in the presence of the PAF antagonists WEB 2086 (100 nM-3 microM) or BN 52021 (100 nM-10 microM). These results indicate a cytotoxic mechanism of histamine release by PAF 100 microM. PAF (10 nM-1 microM) failed to potentiate the mast cell-stimulating activity of anti-IgE, calcium ionophore A23187 or substance P and it did not induce the release of HRFs for skin mast cells when incubated with platelets and leucocytes in concentrations up to 1 microM.
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PMID:Platelet activating factor does not release histamine from human dispersed cutaneous mast cells. 169 68

We studied substance P-induced cutaneous and bronchial reactions in children with allergic disorders. Furthermore, inhibitory effects of lidocaine on these responses elicited by substance P were also studied. In the intradermal test, children with moderate or severe bronchial asthma showed significantly stronger reactions than controls. In bronchial challenge with substance P, children with bronchial asthma showed an increasing fall in FEV1 and V50 in proportion to the severity of their asthma. Concomitant use of lidocaine significantly inhibited not only substance P-induced intradermal erythema and wheal reactions but air flow limitations. It also inhibited histamine-induced erythema and house dust-induced wheal and erythema reactions. No adverse reactions to lidocaine were observed. These results suggest that substance P might play an important role in cutaneous and bronchial hypersensitivity reactions in humans and that lidocaine has an inhibitory effect on substance P-induced reactions.
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PMID:Substance p-induced cutaneous and bronchial reactions in children with bronchial asthma. 170 91

The effects of pretreatment with enalapril, and sulindac, on the weal response to intradermal injections of substance P and neurokinin A were assessed in a randomised, double-blind, placebo-controlled study. Weal responses to both substance P and neurokinin A depended significantly on dose. Neither enalapril nor sulindac, nor the combination of these agents influenced the responses to either tachykinin. These results do not suggest any role for substance P or neurokinin A in the clinical effects of angiotensin converting enzyme inhibitors.
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PMID:The effects of enalapril and sulindac on the dermal response to substance P and neurokinin A. 170 46


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