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)

Stimulation of rat peritoneal mast cells with histamine releasers, such as compound 48/80 and substance P, caused a similar pattern of protein phosphorylations: the molecular weights of the two major phosphorylated proteins were 45 kDa and 59 kDa. When rat mast cells permeabilized with beta-escin were exposed to Ca2+ at concentrations higher than 0.6 microM, phosphorylated proteins of identical molecular weight were also detected. By a radioimmunoprecipitation assay using anti-vimentin mouse monoclonal antibody, the 59 kDa protein was identified as vimentin, one of the intermediate cytoskeletal proteins. Moreover, it became apparent that the phosphoamino acid in phosphorylated vimentin was a serine residue. Sequential changes in vimentin phosphorylation were similar to that of histamine release elicited by histamine releasers: phosphorylation took place within 5 s of stimulation and reached a maximum within 10 s. When permeabilized mast cells were treated with calphostin C, a specific protein kinase C inhibitor, phosphorylation was markedly inhibited. Fluorescence images of mast cells stained with FITC-labelled anti-vimentin antibody showed filamentous structures surrounding the granules in the cytoplasm. However, after exposure to compound 48/80, the filamentous structures promptly disappeared and a dim fluorescence was observed homogeneously in the cell indicating that a rapid depolymerization of vimentin had taken place. From the present study, it became clear that when rat peritoneal mast cells were stimulated, vimentin was rapidly phosphorylated by protein kinase C and this phosphorylation process seems to be related to histamine release.
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PMID:Identification of vimentin in rat peritoneal mast cells and its phosphorylation in association with histamine release. 137 98

Association of 125I-Bolton-Hunter labelled substance P (125I-BH-SP) to suspended pancreatic acinar cells of the guinea pig was studied. Cellular association at 37 degrees C and 22 degrees C was inhibited by cholecystokinin octapeptide (CCK-8) in concentrations from 10(-9) to 10(-6)M, whereas another pancreatic secretagogue, carbachol, was uneffective. The CCK induced inhibition disappeared at low temperatures. CCK-8 mainly interfered with internalization of 125I-BH-SP into acinar cells. Increased extracellular Ca2+ and the Ca2+ ionophores A23187 and ionomycin reduced association of 125I-BH-SP to cells whereas extracellular Ca2+ chelation with EGTA had the opposite effect. However, extra- and intracellular Ca2+ chelation did not affect the degree of CCK-induced reduction of 125I-BH-SP association to acinar cells but eliminated the effect of the calcium ionophore ionomycin. Three agents known to interfere with receptor recycling, namely monensin, methylamine and ammonium chloride reduced cell-associated 125I-BH-SP. In a series of experiments, the cytoplasmic calcium concentrations ([Ca2+]i) during exposure to these three agents, to the CCK-8-analogue caerulein and to ionomycin were determined. In all cases, [Ca2+]i was raised. The results indicate that endocytosis of receptor-bound 125I-BH-SP is regulated by CCK and that the endocytotic process is influenced by calcium.
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PMID:Cholecystokinin-induced inhibition of endocytosis of receptor-bound substance P in pancreatic acinar cells. 138 May 57

The function of nasal polyp mast cells has not been elucidated despite the large number of these cells observed in tissues. We examined these mast cells histochemically, immunohistologically and functionally. Ninety-three percent of collagenase dispersed cells in a nasal polyp were formalin-sensitive. These dispersed cells released histamine in reaction to calcium ionophore A23187 in a dose dependent manner, but not in response to C5a, Compound 48/80 or Substance P. From these results, dispersed mast cells from nasal polyps were considered to be analogous to dispersed mast cells from the human lung and nasal mucosa but not those from human skin. On the other hand, in the reaction with anti-human IgE, dispersed mast cells from a non allergic nasal polyp could not be seen to release histamine. In only 2 of 7 patients, could histamine release in response to Japanese red cedar antigen, from mast cells sensitized passively with the serum of Japanese red cedar pollinosis, seen. Using small tissue samples from polyps, histamine was released by anti-human IgE in allergic patients but not in non allergic patients. Immunohistologically in allergic nasal polyps, some IgE positive mast cells could be seen, whereas in non allergic polyps these cells were absent. These observations suggest that mast cells which had accumulated in nasal polyps both with and without allergy were capable of functional histamine release, whereas in the nasal polyps of allergy patients but not in non-allergic patients these cells are involved in IgE mediated reactions.
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PMID:[Studies on the function of mast cells infiltrating in nasal polyps]. 138 Sep 84

Using intracellular recording, we examined the effects of three mammalian tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), on sympathetic neurons of isolated rat coeliac-superior mesenteric ganglia (C-SMG). The 3 tachykinins elicited two distinct depolarizing responses in ganglion cells: fast depolarization with time-to-peak of 1-2 sec and duration of 5-10 sec, and slow depolarization with time-to-peak of about 20 sec and duration of 120-140 sec. Both fast and slow responses persisted in a solution containing low Ca2+ and high Mg2+ or tetrodotoxin, which indicates that the tachykinins directly act on ganglion cells to produce fast and slow depolarizations. The two types of tachykinin-induced responses exhibited clearly distinguishable properties. The membrane conductance was increased during the fast response, but not significantly changed, slightly decreased or sometimes increased during the slow response. Within certain range of membrane potential, the amplitude of fast response increased upon membrane hyperpolarization and decreased upon depolarization of ganglion cells. In contrast, the amplitude of slow response associated with membrane conductance decrease was increased with membrane depolarization and decreased with hyperpolarization. The fast response was markedly suppressed in a Na(+)-deficient solution, a solution containing nominally zero Ca2+ (plus 0.1 mM EGTA in some cases), and in a solution containing Cd2+ or Mn2+, whereas the slow response was not affected in these solutions and was augmented in some cells in K(+)-free solution. Thus it seems that the increase in Ca(2+)-dependent cationic conductance underlies the fast response and that the slow response is produced at least in part by suppression of certain K+ channels. The fast response progressively decreased in amplitude upon repeated application of the peptides with short intervals, whereas the slow response was rather augmented by repeated application. Lowering the temperature markedly depressed the slow response, while the fast response remained almost unaffected. It is therefore likely that the fast and slow depolarizations are mediated by two different subtypes of tachykinin receptors or a single class of receptors linked with two different intracellular mechanisms. Measurement of tachykinins in several sympathetic ganglia by combined use of HPLC and radioimmunoassay revealed that the highest amount of SP occurs in the C-SMG where the content of SP (136.0 pmol/g protein) was higher than those of NKA (44.3) and NKB (18.7). SP thus appears to function as a major tachykinin in rat C-SMG.
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PMID:Fast and slow depolarizations produced by substance P and other tachykinins in sympathetic neurons of rat prevertebral ganglia. 138 52

Group II phospholipase A2 was detected in appreciable amounts in rat peritoneal mast cells. The effect of several inhibitors specific to 14-kDa group-II phospholipase A2, including two proteinaceous inhibitors and a product of microorganisms with a low molecular mass, on mast-cell activation was examined. When rat peritoneal mast cells were sensitized with IgE and then challenged with antigen, the specific phospholipase-A2 inhibitors suppressed histamine release in a concentration-dependent manner. By contrast, these inhibitors showed no effect on prostaglandin generation under the same conditions. Histamine release from rat peritoneal mast cells subjected to non-immunochemical stimuli, such as concanavalin A, the Ca2+ ionophore A23187, compound 48/80 and substance P was also suppressed. When rat peritoneal mast cells were treated with 14-kDa-group-II-phospholipase-A2-specific inhibitors, washed and stimulated, histamine release was not affected appreciably. Similar suppressive effects of the inhibitors on histamine release were observed with mouse cultured bone-marrow-derived mast cells. When bone-marrow-derived mast cells were activated, they secreted both a soluble and an ecto-enzyme form of 14-kDa group-II phospholipase A2, although appearance of the enzyme associated with the external surface of cells was observed transiently. An appreciable amount of membrane phospholipids was degraded during activation of mast cells, which was decreased by treatment with 14-kDa-group-II-phospholipase-A2 inhibitor. These observations suggest that degranulation and eicosanoid generation in mast cells are regulated independently by discrete phospholipases A2 and that the 14-kDa group-II phospholipase A2 released from mast cells during activation may play an essential role in the progression of the degranulation process.
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PMID:Release of 14-kDa group-II phospholipase A2 from activated mast cells and its possible involvement in the regulation of the degranulation process. 138 85

Depolarization has been shown to alter the biosynthesis of a number of neurotransmitters and neuromodulators. In the rat superior cervical ganglion (SCG), for example, depolarization has been reported to increase catecholamine biosynthesis and to decrease the level of substance P. We have recently found that, although the level of vasoactive intestinal peptide (VIP)-like immunoreactivity (IR) is normally low in the SCG, it increases significantly 48 hr after adult ganglia are deafferented in situ or placed in organ culture. Both manipulations decrease electrical activity of postganglionic neurons. To determine whether the increases in ganglionic VIP-IR could be a consequence of decreased depolarization of sympathetic neurons, the effect of depolarization on the expression of VIP-IR was examined in organ cultures of neonatal and adult SCG. Depolarization with elevated K+ (30 mM) or veratridine (1.5 microM) amplified, rather than blocked, the increases in VIP-IR content seen after 24 hr. Further, it increased the number of detectable VIP-IR neuronal cell bodies and processes. The stimulatory effects of veratridine were prevented by TTX. Since similar changes in expression of VIP-IR were evident in dissociated cell cultures of the SCG, cell-cell interactions requiring intact ganglionic architecture are not necessary for altered peptide expression. Elevating the concentration of Mg2+ blocked the ability of K+ and veratridine to increase VIP-IR in dissociated cell culture, raising the possibility that the effects of depolarization on VIP-IR are mediated by increased Ca2+ entry. The depolarizing conditions that increased VIP-IR also increased substance P-IR. While higher concentrations of veratridine (50 microM) blocked the elevation of both VIP- and substance P-IR induced by explantation, they produced significant neuronal death. Since depolarization with either 30 mM KCl or 1.5 microM veratridine increases expression of VIP-IR in neonatal and adult ganglia, decreased depolarization is unlikely to cause the increases in VIP- and substance P-IR that occur in culture. Furthermore, our data raise the possibility that sympathetic nerve activity in vivo can increase expression of these peptides.
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PMID:Depolarization increases vasoactive intestinal peptide- and substance P-like immunoreactivities in cultured neonatal and adult sympathetic neurons. 138 75

We examined the direct effect of motilin on longitudinal and circular smooth muscle cells isolated from the guinea pig small intestine. In addition, the effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8, an inhibitor of intracellular Ca(2+)-release), verapamil (a voltage-dependent Ca(2+)-channel blocker), and removal of extracellular Ca2+ were investigated to evaluate the role of intracellular Ca2+ stores and extracellular Ca2+ on the muscle contraction induced by motilin. The effects of atropine (a muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and loxiglumide (a CCK-receptor antagonist) were also examined to determine whether the motilin-induced contraction was independent of those receptors. Motilin induced a contraction of the longitudinal and circular smooth muscle cells in a dose-dependent manner with the maximal effect attained after 30 seconds of incubation. The ED50 values were 0.3 nM and 0.05 nM, respectively. TMB-8 suppressed completely the motilin-induced contraction of both types of smooth muscle cells. Verapamil had only a slight suppressive effect. Removal of extracellular Ca2+ did not have any significant influence on motilin-induced contraction. The contractile response to motilin was not affected by atropine, spantide or loxiglumide. Our findings showed that:1) motilin has a direct contractile effect on both longitudinal and circular smooth muscle cells; 2) this contractile effect is not evoked via muscarinic, substance P or CCK receptors, and 3) the intracellular release of Ca2+ plays an important role in the contractile response to motilin on both types of smooth muscle cells.
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PMID:Direct contractile effect of motilin on isolated smooth muscle cells of guinea pig small intestine. 138 65

Bombesin belongs to a family of peptides acting as local hormones with roles in growth regulation, neural function and secretion. Upon binding to its receptor bombesin primarily elicits an increase of inositolphosphates and diacylglycerol, events leading to increased [Ca2+]i and activation of protein kinase C. When asynchronously growing V79 Chinese hamster cells were treated with bombesin in the 10(-9)-10(-7) M concentration range their content of inositolphosphates increased and so did the frequency of mitotic cells with abnormal chromosomal arrangements (c-mitoses). Both effects were abolished by simultaneous addition of the synthetic peptide antagonist D-Arg1,D-Phe5,D-Trpu7,9-Leu11-substance P that binds to certain bombesin receptors. These results demonstrate that the V79 cells most probably have receptors for bombesin and that the weak but significant c-mitotic effect is mediated by such receptors.
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PMID:Bombesin impairs spindle function in mitotic V79 Chinese hamster cells by a receptor-dependent mechanism. 138 41

To investigate the basis of interactions between nerves and mast cells, we tested the actions of the neuropeptide substance P (SP) on whole cell current characteristics of RBL-2H3 cells (homologous to mucosal mast cells). Control RBL cells showed a K(+)-dependent inwardly rectified current. SP (10(-6) M) caused transient, frequently repetitive increases in current amplitude, which at a membrane potential (Vm) of -80 mV rose by -1,020.0 +/- 223.4 pA after SP application compared with -6.8 +/- 1.7 pA for control. This response was characterized by a lag phase of 102 +/- 16 s. Seventeen percent of cells showed spontaneous transients in the current amplitude from the beginning of the recording. After SP administration, the amplitude of these transients increased by 6.3 +/- 2.0-fold. Responses to SP were mimicked by the application of ionomycin. For both SP and ionomycin, there was a dose dependency of the lag phase. Removal of extracellular calcium abolished the response for 10(-6) M SP but not for 6.6 x 10(-6) M ionomycin. During current transients, the whole cell current had both inward and outward rectified components with the zero current Vm shifted from -87.3 +/- 3.2 mV at control to -10.8 +/- 1.7 mV. We compare the SP-evoked current responses in mucosal-type mast cells with those described in connective tissue type.
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PMID:Substance P induces whole cell current transients in RBL-2H3 cells. 138 54

Exogenous administration of lipoxin A4 (LXA4) to guinea pig isolated bronchus produced contractile effects in a concentration-dependent manner (1, 3, and 6 microM). These responses were potentiated when preparations were previously incubated with thiorphan (10 microM), an inhibitor of tachykinin breakdown, but were significantly depressed when sensory nerves were previously desensitized in vitro by capsaicin (10 microM for 15 min) challenge. Ruthenium red (10 microM for 20 min), a blocker of the cationic channel coupled to the capsaicin receptor, also produced, although in a weaker manner, a reduction in bronchomotor responses elicited by LXA4. On the other hand, preexposure to omega-conotoxin (0.1 microM for 45 min), a blocker of neuronal voltage-dependent Ca2+ channels, did not modify the LXA4 contractile effects. Furthermore, LXA4 (6 microM) superfusion of guinea pig bronchial tissue elicited a significant calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) release that was reduced by capsaicin (10 microM, 30 min) desensitization. Finally, LXA4 (10 microM) was unable to displace [3H]resiniferatoxin binding in dorsal root ganglion of rat and guinea pig. These findings support (1) a role for LXA4 in activating motor sensory function of capsaicin-sensitive nerves; (2) this activation mechanism is marginally ruthenium red-sensitive and omega-conotoxin-resistant; and (3) the interaction does not involve the recognized binding site on the vanilloid receptor. As a whole this study presents LXA4 as an endogenous mediator activating sensory nerves potentially involved in basic mechanisms of airway diseases.
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PMID:Pharmacologic and neurochemical evidence for the activation of capsaicin-sensitive sensory nerves by lipoxin A4 in guinea pig bronchus. 138 7


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