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)

Adenosine 5'-triphosphate (ATP) was released into the perfusate of rat isolated mesenteric arterial beds during each of two consecutive increases in flow. There was no significant difference between the amounts of ATP released on each occasion. Substance P was also released into the perfusate by increased flow, although its release was more variable. Removal of the endothelium of the mesenteric vessels with sodium deoxycholate led to a significant reduction (74%) in the amount of ATP released compared with the release before the endothelium had been removed. This suggests that the ATP released into the mesenteric arterial perfusate during increased flow arises from endothelial cells.
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PMID:Flow-induced release of adenosine 5'-triphosphate from endothelial cells of the rat mesenteric arterial bed. 137 Nov 1

In this paper we report the rapid phosphorylation of a cytosolic 100 kDa protein during stimulation of secretion from dispersed aggregates of parotid acinar cells with Ca(2+)-mobilizing secretagogues (carbachol, Substance P, ATP and the Ca2+ ionophore A23187). Phosphorylation was inhibited by removal of extracellular Ca2+ but was not observed during stimulation with phorbol esters, suggesting that this protein is not a substrate for protein kinase C. Two-dimensional PAGE and immunoprecipitation with a specific antiserum indicated that this protein is elongation factor 2, whose Ca2+ calmodulin-dependent phosphorylation has been shown to inhibit protein synthesis [Nairn & Palfrey (1987) J. Biol. Chem. 262, 17299-17303]. These results suggest that phosphorylation of elongation factor 2 is the molecular mechanism for the inhibition of protein synthesis which has been previously observed in rat parotid cells during stimulation with Ca(2+)-mobilizing secretagogues.
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PMID:Phosphorylation of elongation factor 2 during Ca(2+)-mediated secretion from rat parotid acini. 137 3

Indirect evidence links sensory nerves with mast cells (MC) in inflammatory reactions of airway, skin, and intestine. Isolated MC secrete histamine, serotonin, and other inflammatory mediators in response to neuropeptides such as substance P (SP) in vitro. To obtain direct evidence of nerve/MC interactions, we used a tissue culture model involving the co-culture of murine sympathetic neurons and rat basophilic leukemia (RBL) cells (homologous to mucosal MC). An electrophysiologic analysis of the consequences of neuron/RBL cell contacts showed that neurite contact with RBL cells reduced the control input resistance (Ro) of 61.8 +/- 3.2 (n = 110) M omega to 22.4 +/- 4.8 (n = 13) M omega (P less than 0.01) without change in the membrane potential. Time course studies showed that Ro of RBL cells with neurite contact was always lower by 30 to 54% than adjacent RBL cells lacking such contact. This effect was not seen in RBL cells cultured on rat fibroblasts. Direct application of SP, bradykinin, and somatostatin, but not acetylcholine, noradrenaline, or the putative neurotransmitter ATP, could partly mimic the effect of neurite contact. Therefore, neurotransmitter release from sympathetic neurons in contact with RBL cells may decrease RBL cell membrane resistance, possibly leading to activation.
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PMID:Sympathetic nerve contact alters membrane resistance of cells of the RBL-2H3 mucosal mast cell line. 137 18

This study compared the effects of endothelin-1 (ET-1), ET-2 and ET-3 on the guinea pig field-stimulated ileum. All ETs (0.3-30 nM) caused graded inhibitions of nerve-mediated responses followed by sustained contractions. The rank order of potencies for the twitch depressor effect (IC50S) was ET-3 = ET-1 greater than ET-2, with ET-3 causing greater maximal inhibition than ET-1 or ET-2. The rank order of potencies for contraction (EC50S) was ET-1 = ET-2 greater than ET-3, with ET-1 causing greater maximal contraction than ET-2 or ET-3. Twitch inhibition by ET-1 (3 nM) was unaffected by indomethacin (5.6 microM), cromakalim (10 microM), glibenclamide (3 microM) or nicardipine (0.1 microM). ET-1-induced contraction was unaltered by tetrodotoxin (0.3 microM), atropine (0.3 microM) or glibenclamide, but was reduced by indomethacin. Cromakalim and nicardipine virtually abolished ET-1-induced contraction. ET-1 (up to 30 nM) did not potentiate submaximal contractions induced by acetylcholine, histamine, bradykinin or substance P. ET-3 relaxed ileal segments precontracted with either acetylcholine (0.3 microM) or histamine (1 microM). Pretreatment of guinea pigs with pertussis toxin (50 micrograms/kg i.p., 6 days beforehand) did not influence either effects of ET-1 on the field-stimulated ileum. Our data suggest that the dual effects of ETs on the guinea pig isolated ileum are mediated by distinct receptors and possibly involve different mechanisms of action. The transient inhibition of responses to field stimulation seems unrelated to activation of ATP-sensitive potassium channels and is rather insensitive to L-type Ca++ channel blockade.
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PMID:Dual effects of endothelins -1, -2 and -3 on guinea pig field-stimulated ileum: possible mediation by two receptors coupled to pertussis toxin-insensitive mechanisms. 137 59

1. The effects of L-NG-nitroarginine (L-NOARG) and L-NG-nitroarginine methyl ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig coronary bed, by use of a Langendorff technique. The effects of these inhibitors of nitric oxide synthesis were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The vasodilator responses evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L-NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x 10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(-7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature, the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and bradykinin appear to involve other mechanisms in addition to the release of nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the vasodilator actions of 5-HT and ATP in this preparation.
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PMID:Effects of nitric oxide synthase inhibitors, L-NG-nitroarginine and L-NG-nitroarginine methyl ester, on responses to vasodilators of the guinea-pig coronary vasculature. 138 16

The present work was undertaken to determine by immunocytochemical methods which of the putative enteric neurotransmitters are contained in axons supplying the guinea-pig taenia coli and what proportion of axons is accounted for by the presence of these substances. Numerous fibres displayed immunoreactivity for dynorphin (DYN), enkephalin (ENK), gamma-aminobutyric acid (GABA), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in contrast to other gut regions, fibres showing immunoreactivity for gastrin-releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5-hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like immunoreactivity (TH-LI) was present in numerous fibres that disappeared after extrinsic denervation, a procedure that did not detectably affect any of the other major groups of fibres. Simultaneous staining of extrinsically denervated preparations revealed that SP-LI and VIP-LI were located in separate fibres, and ultrastructural studies showed these to be 58% and 33% of intrinsic fibres supplying the muscle. Immunoreactivity for the general marker, neuron-specific enolase, was located in 95-98% of axons. ENK-LI and DYN-LI were in the same axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about 85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI fibres, were reactive for NOS. The results imply that the taenia of the guinea-pig caecum is innervated by two major groups of enteric neurons: (i) excitatory neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases, the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained in a smaller population of intrinsic axons. Even though the taenia represents one of the simplest tissues for examining transmission from enteric neurons to intestinal muscle, it shares some of the complexity of other regions, in that four major axon types supply the muscle and both the enteric excitatory and enteric inhibitory neurons contain multiple transmitters.
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PMID:Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum. 138 81

Xerostomia, the subjective feeling of dry mouth, affects millions of people particularly the elderly. It is invariably associated with hypofunction of the salivary glands. The amount, rate of secretion, and composition of saliva are regulated by both sympathetic and parasympathetic receptor systems whose stimulation transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Salivary glands express a variety of cell-surface receptors including adrenergic (alpha and beta), muscarinic-cholinergic, substance P, vasoactive intestinal peptide hormone, and ATP receptors. Ascorbate which is present in salivary acinar cells in relatively high concentrations, is closely involved in many cellular functions including the metabolism of pyrimidines, intracellular calcium, the catecholamines and other neurotransmitters which regulate salivary gland exocytosis. Ascorbate-dependent carboxyl-terminal peptide alpha-amidation enzyme similar to the pituitary peptidyl-glycine alpha-amidating monooxygase, is also present in salivary glands. It is therefore not fortuitous that the seemingly unrelated numerous factors like aging, drug ingestion, pregnancy, smoking, ionizing radiation, stress, and various pathological states such as cancer, autoimmune disorders, diabetes mellitus, and hypertension often implicated in the causation of xerostomia, all promote increased tissue requirement for and/or depletion of ascorbate.
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PMID:Ascorbate status and xerostomia. 143 93

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart. 150 17

Spontaneous oscillations in intracellular Ca2+ concentration ([Ca2+]i) and membrane potential were used to monitor rhythmicity in freshly dispersed and cultured interstitial cells (IC) from the canine colon. The frequency of oscillations and responses to a number of channel blockers, agonists, ionic substitutions, and temperature were similar in freshly dispersed and cultured cells. An increase in the amplitude of Ca2+ oscillations after 3-6 days in culture and an increase in the rate of decline of [Ca2+]i in cultured IC were two differences noted between freshly dispersed and cultured cells. The frequency and amplitude of oscillations were a function of extracellular Ca2+ concentrations, and oscillations were abolished when the transmembrane flux of Ca2+ was reduced by nicardipine, La3+, or removal of Ca2+ from the extracellular medium. Oscillations persisted in the presence of ryanodine and ouabain. Lowered temperatures or a reduction in the concentration of Ca2+ in the medium reduced the frequency of spontaneous oscillations. Carbachol and substance P caused a transient increase in [Ca2+]i. Substance P then abolished spontaneous events. ATP and calcitonin gene-related peptide increased the frequency of spontaneous activity. Vasoactive intestinal peptide caused a temporary delay in spontaneous oscillations when added to the medium. Results indicate that freshly dispersed and cultured IC may be useful in studies of the mechanisms of rhythmicity in the gastrointestinal system.
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PMID:Calcium oscillations in freshly dispersed and cultured interstitial cells from canine colon. 155 Feb 5

The effects of 1-methyl-4-phenylpyridinium (MPP+) were studied in rat striatum. Using freeze-clamp, microwave, and water-suppressed proton chemical shift magnetic resonance imaging techniques, MPP+ resulted in marked increases in lactate and a depletion of ATP for up to 48 h after the injections. MPP+ produced dose-dependent depletions of dopamine, serotonin, gamma-aminobutyric acid, and substance P that were partially blocked at 1 week by prior decortication or completely blocked by MK-801 at 24 h. The lesions showed relative sparing of somatostatin-neuropeptide Y neurons, consistent with N-methyl-D-aspartate (NMDA) excitotoxicity. MPP+ produces impairment of oxidative phosphorylation in vivo, which may result in membrane depolarization with persistent activation of NMDA receptors and excitotoxic neuronal degeneration. An impairment of energy metabolism may therefore underlie slow excitotoxic neuronal death in neurodegenerative diseases.
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PMID:1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. 156 Feb 46


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