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 mechanisms underlying the ability of substance P, to stimulate the sn-1,2-diacylglycerol (DAG) formation were studied using rat parotid acinar cells. During a 60 s stimulation, 1 microM substance P caused a rapid rise in DAG accumulation at 5 s, whereas a low (0.1 microM) concentration of agonist did not. During long term stimulation for 30 min, DAG accumulation induced by 1 microM substance P reached near maximal levels at 5 min and remained elevated for at least 20 min. In contrast, DAG formation induced by 0.1 microM substance P exhibited a peak at 5 min, gradually declined and returned to near basal levels at 30 min. Furthermore, DAG accumulation in response to substance P at 5 and 20 min increased in a dose-dependent manner. The breakdown of both [32P]phosphatidylinositol 4-monophosphate ([32P]PIP) and [32P]phosphatidylinositol 4,5-bisphosphate ([32P]PIP2) stimulated by 1 microM substance P significantly increased from 5 to 20 min and returned to basal levels by 30 min; however, the breakdown of [32P]PIP2 was greater than that of [32P]PIP. At a low concentration of substance P, [32P]PIP2 breakdown reached maximal levels at 5 min followed by a progressive decrease and returned to basal levels at 30 min, whereas the breakdown of [32P]PIP reached maximal levels at 5 min and returned to near basal levels at 10 min. Both concentrations of substance P caused some [32P]phosphatidylinositol breakdown at 5 min. Changes in [3H]inositol trisphosphate induced by substance P were similar to those in [32P]PIP2. In addition, substance P (1 microM) did not stimulate the release of [3H]choline or [3H]ethanolamine metabolites into the medium. Substance P-induced DAG formation was not inhibited by staurosporine, a protein kinase C inhibitor. These results suggest that DAG formation caused by substance P is closely associated with the hydrolysis of phosphatidylinositides but not that of phosphatidylcholine or phosphatidylethanolamine, and is not regulated by protein kinase C-dependent mechanism(s).
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PMID:Substance P-induced diacylglycerol formation in rat parotid acinar cells. 172 87

1. Cigarette smoke induces plasma exudation in the airways of rodents by activation of capsaicin-sensitive 'sensory-efferent' nerves. The response is mediated predominantly by substance P (SP) and the magnitude of exudation is regulated by neutral endopeptidase (NEP). The component(s) of the smoke responsible for the activation of the nerves may be reactive oxygen radicals. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea (DMTU), a regulator of superoxide anion, superoxide dismutase (SOD), and a regulator of hydrogen peroxide, catalase, on plasma exudation (measured using Evans blue dye) induced by cigarette smoke in guinea-pig main bronchi in vivo. The effect of DMTU on plasma exudation and non-cholinergic bronchoconstriction (measured as pulmonary insufflation pressure, PIP) induced by electrical stimulation of the vagus nerves was also assessed. Interaction between hydroxyl radicals and NEP was assessed with the NEP inhibitor phosphoramidon. 2. In each of the experiments, cigarette smoke increased plasma exudation by approximately 200% above air-exposed controls. Acute administration of DMTU (1.5 g kg-1, i.v. for 20 min) significantly reduced cigarette smoke-induced plasma exudation by 69%. In contrast, neither SOD (240,000 u kg-1, i.v.) nor catalase (400,000 u kg-1, i.v.) significantly affected the exudative response. 3. Chronic pretreatment with DMTU (1.25 g kg-1 over 4 days) significantly reduced bronchial plasma exudation induced by cigarette smoke by 72%. Phosphoramidon (1.5 mg kg-1, i.v.) completely reversed the inhibition by DMTU of cigarette smoke-induced plasma exudation. 4. Vagal stimulation increased plasma exudation by approximately 200% and PIP by approximately 250%. Acute treatment with DMTU had no significant inhibitory effect on these responses, whereas chronic pretreatment inhibited them by approximately 80%. Phosphoramidon reversed the inhibition by chronic DMTU. 5. SP (1 nmol kg-1) increased plasma exudation by approximately 250%, a response which was not inhibited by either acute or chronic DMTU. 6. We conclude that hydroxyl radicals, rather than superoxide anion or hydrogen peroxide, are involved in the induction of neurogenic plasma exudation and bronchoconstriction induced by cigarette smoke or by electrical stimulation of the vagus nerves. These radicals also affect the activity of NEP. Acute DMTU may affect directly the neural actions of hydroxyl radicals contained in the cigarette smoke. Chronic pretreatment with DMTU may inhibit the neurogenic airway responses by effects on tachykinin biosynthesis and/or axonal transport.
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PMID:Involvement of hydroxyl radicals in neurogenic airway plasma exudation and bronchoconstriction in guinea-pigs in vivo. 882 33

Substance P (SP) plays an important role in sensitization of spinal cord neurons. In this study, we investigated SP-induced calcium activities in cultured rat spinal cord neurons with confocal laser scanning microscopy. Our results showed that SP increased [Ca(2+)](i) by calcium entry rather than release from intracellular calcium stores. Neomycin (100 microM), an antagonist of phosphatidylinositol 4,5-bisphosphate (PIP(2)), blocked SP-induced calcium entry. Ca(2+)-free medium induced capacitative entry, which was significantly potentiated by SP. As activation of SP receptor (NK-1) leads to production of inositol 1,4,5-trisphosphate (IP(3)) by PIP(2) turnover, the results indicates that SP-induced calcium entry and SP-potentiated capacitative calcium entry might be mediated or regulated by IP(3)/diacylglycerol (DG) pathway.
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PMID:Neomycin blocks substance P-induced calcium entry in cultured rat spinal cord neurons. 1084 90

Certain transmitters inhibit Kir3 (GIRK) channels, resulting in neuronal excitation. We analysed signalling mechanisms for substance P (SP)-induced Kir3 inhibition in relation to the role of phosphatidylinositol 4,5-bisphosphate (PIP(2)). SP rapidly - with a half-time of approximately 10 s with intracellular GTPgammaS and approximately 14 s with intracellular GTP - inhibits a robustly activated Kir3.1/Kir3.2 current. A mutant Kir3 channel, Kir3.1(M223L)/Kir3.2(I234L), which has a stronger binding to PIP(2) than does the wild type Kir3.1/Kir3.2, is inhibited by SP as rapidly as the wild type Kir3.1/Kir3.2. This result contradicts the idea that Kir3 inhibition originates from the depletion of PIP(2). A Kir2.1 (IRK1) mutant, Kir2.1(R218Q), despite having a weaker binding to PIP(2) than wild type Kir3.1/Kir3.2, shows a SP-induced inhibition slower than the wild type Kir3.1/Kir3.2 channel, again conflicting with the PIP(2) theory of channel inhibition. Co-immunoprecipitation reveals that Galpha(q) binds with Kir3.2, but not with Kir2.2 or Kir2.1. These functional results and co-immunoprecipitation data suggest that G(q) activation rapidly inhibits Kir3 (but not Kir2), possibly by direct binding of Galpha(q) to the channel.
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PMID:Signal transduction pathway for the substance P-induced inhibition of rat Kir3 (GIRK) channel. 1573 Nov 96