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)

Strip preparations of human epicardial coronary arteries (free of atherosclerosis) relaxed in an endothelium-dependent fashion to substance P and Ca2+-ionophore A23187. Acetylcholine generally caused contraction in the same strips. Glyceryl trinitrate and isoproterenol induced relaxation irrespective of the presence or absence of endothelium. Nordihydroguaiaretic acid abolished the relaxation produced by substance P and A23187. Mepacrine only blocked substance P relaxation. Haemoglobin and methylene blue inhibited substance P and A23187 relaxations but also reduced the response to glyceryl trinitrate. These inhibitor experiments indicate that human coronary arteries are relaxed by the endothelium-derived relaxing factor.
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PMID:Endothelium-dependent relaxation of human epicardial coronary arteries: frequent lack of effect of acetylcholine. 243 15

Guinea pigs were inoculated by nasal insufflation with parainfluenza 3 (P-3) or virus growth medium 4 days before performing in vitro pharmacologic studies on left bronchial ring segments. Cumulative dose-response studies with capsaicin revealed an enhanced contractile response after P-3 infection. The sensitivity and magnitude of contractile effects of substance P in the left bronchi were also enhanced by P-3 infection. After pretreatment of the isolated tissues with phenoxybenzamine to block histamine H1 (with metiamide to block histamine H2), muscarinic, serotonergic, and alpha adrenergic receptors, or indomethacin to block the cyclooxygenase pathway of arachidonic acid metabolism, P-3 remained effective in enhancing contractile responses, even though these pretreatments altered the sensitivity and/or magnitude of contractions produced by substance P. When ETYA or NDGA were combined with indomethacin to also block the lipoxygenase pathway of arachidonic acid metabolism, the sensitizing effect of P-3 infection was diminished or abolished, especially at larger concentrations of substance P. With combination of FPL55712 and indomethacin, the sensitizing effect of P-3 was not abolished. Contractile responses to LTC4 and LTD4 were not enhanced by P-3 infection. The data suggest a selective influence of P-3 infection on the substance P system and provide evidence for a role of the lipoxygenase pathway of arachidonic acid metabolism in the sensitizing action. Peptide leukotrienes do not appear to be the lipoxygenase products involved in this effect of virus.
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PMID:Enhancement by parainfluenza 3 infection of contractile responses to substance P and capsaicin in airway smooth muscle from the guinea pig. 244 48

The role of endothelium on the responses of the perfused rabbit renal artery segments to vasoconstrictor and vasodilator agents was studied. The vasoconstrictor responses of rabbit renal arteries to phenylephrine were enhanced by endothelium destruction. Acetylcholine (ACh), calcium-ionophore (A23187) and substance P (SP), in the presence of indomethacin, induced endothelium-dependent vasodilation of the phenylephrine-constricted renal arteries. Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, significantly reduced the dilator responses to ACh, A23187 and SP, but did not reduce the responses to sodium nitrite. In conclusion, our results provide evidence for the involvement of lipoxygenase products in the endothelium-dependent vasodilation of rabbit renal arteries to ACh, A23184 and SP.
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PMID:Endothelium-dependent vasodilator actions of acetylcholine, calcium-ionophore (A23187) and substance P in perfused renal arteries from rabbits. 245 9

Substance P (SP) is an important neuropeptide involved in neurogenic inflammation and most of its pathophysiological functions are mediated through binding to the neurokinin-1 receptor. SP exerts various proinflammatory actions on immune-cells, including macrophages. Several compounds such as cytokines have the capacity to activate and stimulate macrophages to produce arachidonic acid oxygenation and lipoxygenation products. Leukotriene B4 (LTB4) is one of the most important mediators of leukocyte activation in acute and chronic inflammatory reactions. LTB4 stimulates chemotaxis, lysosomal enzyme release, and cell aggregation. In this report, we studied the effect of SP on rat adherent granuloma macrophages (RAGMs). The chronic granuloma in rat was induced by dorsal injections of a potassium permanganate (KMnO4) saturated crystal solution (200 microl of a 1:40 dilution). After 7 days, all rats developed a subcutaneous granuloma in the injection site from which infiltrated macrophages were extracted, isolated, and cultured in vitro. We tested the hypothesis that SP stimulates the production of LTB4 in RAGMs and increases lipoxygenase expression. Here we show that the cell-free supernatant of RAGMs stimulated with SP (10 microM), resulted in statistically significant increases of LTB4 Preincubation of RAGMs with NDGA (nordihydroguaiaretic acid (10 microM), completely abolished the production of LTB(4) in the supernatants and lipoxygenase expression on RAGMs challenged with SP, or the cation ionophore A23187 (positive control). Similar effects were obtained when the cells were pretreated with dexamethasone (10 microM). Our results suggest that SP is able to stimulate the release of LTB4 and lipoxygenase expression in macrophages from chronic inflammatory granuloma and provide further evidence for a neuroinflammatory pathway.
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PMID:Substance P upregulates LTB4 in rat adherent macrophages from granuloma induced by KMnO4. 1938 87

This study tests the hypothesis that the lipoxygenase (LOX) pathway mediates protease-activated receptor (PAR) 2-induced activation of the transient receptor potential vanilloid receptor 1 (TRPV1) to protect the heart from ischemia/reperfusion (I/R) injury. SLIGRL, a PAR2 activating peptide, was administered prior to reperfusion following left anterior descending coronary artery ligation in wild type (WT) and TRPV1 knockout (TRPV1-/-) mice. In a Langendorffly perfused heart I/R model, hemodynamic parameters, including left ventricular end-diastolic pressure, left ventricular developed pressure, coronary blood flow and left ventricular peak +dP/dt were evaluated after I/R. SLIGRL reduced the cardiac infarct size in WT and TRPV1-/- mice with a greater effect in the former strain (P<0.05). SLIGRL increased plasma levels of calcitonin gene-related peptide (CGRP) and substance P in WT (both P<0.05) but not in TRPV1-/- mice. Pretreatment with CGRP8-37 (a CGRP receptor antagonist) or RP67580 (a neurokinin-1 receptor antagonist) alone had no effect on SLIGRL-induced cardiac protection in either strain. However, combined administration of CGRP8-37 and RP67580 abolished SLIGRL-induced cardiac protection in WT but not in TRPV1-/- mice. Nordihydroguaiaretic acid (a general LOX inhibitor) and baicalein (a 12-LOX inhibitor), but not indomethacin (a cyclooxygenase inhibitor) and hexanamide (a selective cytochrome P450 epoxygenase inhibitor), abolished the protective effects of SLIGRL in WT (all P<0.05) but not in TRPV1-/- hearts. These data suggested that PAR2, possibly via 12-LOX, activates TRPV1 and leads to CGRP and substance P release to prevent I/R injury in the heart, indicating that the 12-LOX-TRPV1 pathway conveys cardiac protection to alleviate myocardial infarction.
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PMID:Protease-activated receptor 2 protects against myocardial ischemia-reperfusion injury through the lipoxygenase pathway and TRPV1 channels. 3160 41