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 responses of human labial salivary acini to muscarinic, adrenergic, and substance P peptidergic stimulation were studied using the fluorescent indicators fura 2 for intracellular Ca2+ concentration ([Ca2+]i) and sodium-binding benzofuran isophthalate for intracellular Na+ concentration ([Na+]i). Of the agents tested (carbachol, epinephrine, isoproterenol, and substance P) only the muscarinic agonist carbachol increased [Ca2+]i substantially above basal levels (three to fourfold; half-maximal effect approximatley 1 microM). Experiments with the Ca(2+)-adenosinetriphosphatase inhibitor thapsigargin indicated the presence of both thapsigargin-sensitive and thapsigargin-insensitive intracellular Ca2+ stores, both of which were mobilized by carbachol. [Na+]i in resting labial acini was approximately 20 mM. On stimulation with carbachol, [Na+]i rose transiently to more than three times this value and then partially recovered. This carbachol-induced rise in [Na+]i was largely blocked by bumetanide, a specific inhibitor of the Na(+)-K(+)-2Cl- cotransporter. These results are consistent with an intact muscarinic fluid secretory response in human labial acini with transepithelial Cl- secretion driven via Na(+)-K(+)-2Cl- cotransport and the secretion of fluid presumably following Cl- loss via an apical Ca(2+)-dependent anion channel, as observed in salivary acini from other species.
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PMID:Microfluorometric studies of intracellular Ca2+ and Na+ concentrations in normal human labial gland acini. 794 25

The purpose of the present study was to examine Ca2+ signaling mechanisms in Sf9 cells and to demonstrate expression and functional linkage of a mammalian receptor to changes in cytosolic free Ca2+ concentration ([Ca2+]i). Addition of p-octopamine (50 microM to fura 2-loaded Sf9 cells produced a small transient increase in [Ca2+]i from a basal level of 58 +/- 10 to 194 +/- 7.6 (SD) nM. The response to octopamine was inhibited by both cyproheptadine and chlorpromazine and was mimicked by clonidine. In contrast, [Ca2+]i did not change in response to dopamine (50 microM), substance P (50 nM), histamine (50 microM), ATP (50 microM), acetylcholine (10 or 100 microM), carbachol (10 or 100 microM), serotonin (50 microM), epinephrine (10 microM), or bradykinin (50 nM). The Ca(2+)-adenosinetriphosphatase inhibitors thapsigargin (200 nM) and 2,5-di-tert-butylhydroquinone (BHQ; 10 microM) increased [Ca2+]i to 307 +/- 13 and 137 +/- 20 nM, respectively. In contrast to BHQ, the response to thapsigargin was attenuated by La3+ or removal of extracellular Ca2+ and increased by elevation of extracellular Ca2+. These results suggest that thapsigargin but not BHQ stimulates Ca2+ influx. The rat brain muscarinic receptor (subtype M5) was incorporated into the baculovirus by homologous recombination. Addition of carbachol (100 microM) increased [Ca2+]i from 92.7 +/- 6.4 to 480 +/- 26 nM in Sf9 cells infected with recombinant virus containing the M5 receptor cDNA. The effect of carbachol on [Ca2+]i was concentration dependent with a 50% effective concentration of approximately 30 microM and was blocked by atropine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ca2+ signaling in Sf9 insect cells and the functional expression of a rat brain M5 muscarinic receptor. 802 3

Application of substance P (SP), a potent endothelium-dependent vasodilator, to porcine coronary artery endothelial cells (PCAECs) results in release of Ca2+ from intracellular stores followed by extracellular Ca2+ influx. We tested the hypothesis that intracellular store depletion results in tyrosine phosphorylation, which promotes Ca2+ influx. PCAECs labeled with antiphosphotyrosine antibody conjugated to fluorescein isothiocyanate showed a 3.3- to 3.4-fold increase in fluorescence in response to SP or 2,5-di-tert-butylhydroquinone (BHQ), an agent that depletes intracellular stores by inhibiting the endoplasmic reticulum Ca(2+)-adenosinetriphosphatase. In both cases, the tyrosine kinase inhibitor, genistein, reduced the fluorescence intensity to near-basal levels. Pretreatment of PCAECs with the tyrosine kinase inhibitors, genistein or tyrphostin, induced a significant reduction in the plateau phase of SP-induced Ca2+ elevation with no effect on the release of Ca2+ from stores. Neither daidzein, a structurally similar but inactive analogue of genistein, nor H-7, a serine-threonine kinase inhibitor, affected SP-induced Ca2+ influx. Voltage-clamp recordings using the perforated patch technique with simultaneous Ca2+ measurements showed that intracellular Ca2+ elevation and inward current activated by SP and BHQ were reduced by 60-70% in response to genistein. These data indicate that the link between store depletion and Ca2+ influx in endothelial cells requires tyrosine phosphorylation.
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PMID:Calcium entry activated by store depletion in coronary endothelium is promoted by tyrosine phosphorylation. 876 61

Isolated myenteric ganglion networks were prepared from guinea pig ileum and were used in a perifusion protocol to examine the effects of interstitial adenosine on evoked release of substance P-like immunoreactivity (SPLI). The release of SPLI evoked by elevated extracellular K+ concentration was increased in the presence of tetrodotoxin (TTX), indicating tonic inhibition of SPLI release and revealing net inhibitory interganglionic transmission. Perifusion in the presence of the adenosine A1 receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine enhanced evoked SPLI release, which was further enhanced in the additional presence of TTX, indicating that adenosine contributes some, but not all, of the overall inhibitory tone within the networks. In addition to neural release of adenosine per se, an additional source was investigated. Perifusion in the presence of alpha, beta-methylene-ADP plus guanosine 5'-monophosphate, which inhibits ecto-adenosinetriphosphatase (ATPase) activity, enhanced SPLI release, indicating that hydrolysis of released ATP contributes to the total interstitial nucleoside concentration and thereby to the overall inhibitory tone. It is concluded that endogenous adenosine, some of which arises from ATP metabolism, is an important contributor to the overall inhibitory tone present in myenteric ganglion networks.
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PMID:Endogenous adenosine inhibits evoked substance P release from perifused networks of myenteric ganglia. 903 74