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)

Histamine at concentrations higher than 10(-9) M significantly elicited cortisol secretion from bovine adrenocortical (BAC) cells co-incubated with bovine adrenal medullary (BAM) cells, suggesting that BAM cells are responsible for histamine-induced cortisol secretion. Cortisol secretion from BAC cells co-incubated with BAM cells was also elicited by both an H1 agonist, 2-methylhistamine, and an H2 agonist, 4-methylhistamine. However, 4-methylhistamine was much less effective than 2-methylhistamine. Histamine-induced cortisol secretion was inhibited not only by H1 antagonists (pyrilamine and diphenhydramine) but also by H2 antagonists (cimetidine and ranitidine). Histamine effectively increased 45Ca uptake and IP3 production in BAM cells. These responses were antagonized by the H1 antagonist but not by the H2 antagonist. Histamine-induced cortisol secretion from BAC cells co-incubated with BAM cells was inhibited by beta-adrenoceptor antagonists, propranolol and timolol, as well as an NK1-receptor antagonist, D-Arg1-D-Trp7,9-Leu11-substance P. These results indicate that histamine can induce cortisol secretion from BAC cells at physiological concentrations through H1 receptors on BAM cells, and catecholamine and substance P may participate in histamine-induced cortisol secretion.
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PMID:Histamine-induced cortisol secretion from bovine adrenocortical cells: co-incubated with bovine adrenal medullary cells. 941 25

The in vivo bronchoconstrictor effect of tachykinins in Fisher 344 rats is accompanied by release into the airways of 5-hydroxytryptamine (5-HT). 5-HT is possibly derived from mast cells. In the present study the presumed mast cell-tachykinin interaction was studied in isolated trachea from Fisher 344 rats. Contractions induced by neurokinin A were largely reduced by the 5-HT antagonist methysergide, partially reduced by atropine, but not affected by hexamethonium or tetrodotoxin. Methysergide also inhibited the contractions induced by substance P, the tachykinin NK1 receptor agonist Ac[Arg6, Sar9, Met(O2)11]substance P-(6-11) and the mast cell depleting compound 48/80. Methysergide had no effect on contractions induced by carbachol or electrical field stimulation. Atropine significantly reduced contractions to 5-HT and completely inhibited contractions induced by electrical field stimulation. Histamine had no contractile effect. In vivo pretreatment with compound 48/80 significantly reduced the in vitro contractions to neurokinin A. Contractions to capsaicin were inhibited by methysergide and the tachykinin NK1 receptor antagonist (+/-)-RP67580 ((3alphaR,7alphaR)-(7,7-diphenyl-2-(1-imino-2-(2-methoxyp henylethyl)-perhydraisoinotol-4-one))). Substance P and neurokinin A caused 5-HT release in the organ bath, in a concentration- and time-dependent way. Atropine did not affect 5-HT release. Morphometric analysis showed that substance P and neurokinin A, but not carbachol, caused a significant increase in the number of degranulating mast cells in the muscular/submuscular region. In conclusion, tachykinins contract Fisher 344 rat trachea by releasing 5-HT from mast cells, an effect mediated by a tachykinin NK1 receptor.
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PMID:Role of 5-hydroxytryptamine and mast cells in the tachykinin-induced contraction of rat trachea in vitro. 942 20

The effects of histamine and N(alpha)-methylhistamine, two components of gastric juice, on vagal and transmural stimulation of the guinea-pig isolated oesophagus were compared with their effects on cholinergic and on non-adrenergic-non-cholinergic (NANC) neuronal responses in the isolated ileum, both tissues having been pretreated with mepyramine (1 microM). Histamine (< or = 10 microM) and N(alpha)-methylhistamine (< or = 1 microM) had no significant effect on either vagal or transmural stimulation in the oesophagus. Substance P, which produces a contraction by activation of cholinergic nerves in the oesophagus also was unaffected by histamine. In contrast, the agonists inhibited contractions produced by cholinergic nerve stimulation in the ileum; the inhibition produced by histamine (10 microM) was up to 73 +/- 5%, that by N(alpha)-methylhistamine (1 microM), 48 +/- 5%. Histamine also inhibited responses to stimulation of NANC neurons by up to 37 +/- 14%. The effects of histamine and N(alpha)-methylhistamine in the ileum were inhibited by clobenpropit (0.1 microM). These findings suggest that histamine and N(alpha)-methylhistamine have no role in the modulation of neuronal function in the oesophagus, in contrast with their effect in the ileum.
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PMID:Comparison of the effects of histamine and N(alpha)-methylhistamine on neuronal function in the guinea-pig oesophagus and ileum. 946 46

The role of substance P in experimental allergic conjunctivitis induced by egg albumin was investigated with guinea pigs. Increase in vascular permeability of the conjunctiva induced by antigen was significantly inhibited after repeated application of capsaicin. Substance P contents in the conjunctiva of guinea pig were decreased by topical instillation of antigen to the eyes, suggesting that substance P was released from the conjunctiva due to antigen-antibody reaction. Moreover, subconjunctival injection of substance P resulted in a dose-related conjunctivitis, and vascular permeability in the conjunctiva was also increased by substance P. In substance P-induced conjunctivitis, a significant edema was observed in the bulbar and palpebral conjunctiva, but no hyperemia was noted in all instances. Histamine contents of the conjunctiva and tears were not influenced by subconjunctival injection of substance P. However, topical application of antigen and subconjunctival injection of compound 48/80 caused a significant decrease in histamine content, and content of tear was increased by both treatments. An increase in vascular permeability induced by antigen application was significantly inhibited by intravenous injection of FK-888, which is a specific and potent NK1 receptor antagonist. From these results, it is suggested that substance P is responsible for allergic conjunctivitis to some extent, and the conjunctival hyperpermeability induced by substance P occurs through NK1 receptor on the blood vessels, rather than by the direct action on the conjunctival mast cells during allergic conjunctival reactions.
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PMID:Role of substance P in experimental allergic conjunctivitis in guinea pigs. 950 Jan 28

1. In human U373 MG astrocytoma cells agonist-induced increases in intracellular Ca2+ ([Ca2+]i) are rapidly returned towards prestimulated levels. Examination of the effect of histamine and substance P on [Ca2+]i in thapsigargin-treated cells has allowed a mechanism contributing to this effect to be characterized. 2. Histamine and substance P stimulated [3H]-inositol monophosphate ([3H]-IP1) accumulation in U373 MG cells. Concentration-response curves of [3H]-IP1 accumulation in suspensions of U373 MG cells in HEPES buffer containing 30 mM Li+ yielded best-fit EC50 values of 19.1+/-1.5 microM for histamine and 5.7+/-1.3 nM for substance P. 3. In confluent monolayers of fura-2 loaded U373 MG cells perfusion with 100 microM histamine resulted in a transient 597+/-50 nM increase in [Ca2+]i. The best-fit EC50 for histamine was 4.6+/-2.2 microM. The initial, transient, histamine response was often followed by further small transient increases in [Ca2+]i. 4. Treatment of U373 MG cells with 5 microM thapsigargin, followed by the readdition of 1.8 mM Ca2+ to the perfusion buffer, resulted in a steady-state level of [Ca2+]i 97+/-5 nM above pretreated levels (measured 400 s after readdition of Ca2+). Perfusion of histamine (100 microM, 100 s) caused a rapid decline in the thapsigargin-induced steady state level of [Ca2+]i. This effect of histamine was normally reversible upon washout. The best-fit EC50, for the histamine response was 0.8+/-0.2 microM. Substance P (10 nM, 100s) also caused a reduction in thapsigargin-induced steady-state levels of [Ca2+]i. 5. Neither 100 microM histamine nor 10 nM substance P inhibited the rate of quench of fura-2 fluorescence by Mn2+ in U373 MG cells pretreated with 5 microM thapsigargin, indicating that the depressant effect on steady-state raised [Ca2+]i was probably not due to a block of Ca2+ entry. 6. The depressant effect of histamine on [Ca2+]i was blocked by 1 microM mepyramine, and was partially reduced by pre-incubation with 1 microM staurosporine (61+/-7% reduction) and with Ro 31-8220 (24+/-10% and 50+/-6% reduction by 1 and 10 microM Ro 31-8220, respectively). Pre-incubation with H-89 did not alter the depressant effect of histamine. 7. Neither 1 microM staurosporine nor 10 microM KN-62 inhibited the binding of [3H]-mepyramine to guinea-pig cerebellar membranes, whereas it was reduced by 17+/-1% and 55+/-2% by 1 and 10 microM Ro 31-8220, respectively. However, [3H]-IP1 accumulation stimulated by histamine in U373 MG cells was not inhibited by 1 or 10 microM Ro 31-8220 and in 2 out of 3 experiments there was a significant potentiation of the response to histamine with both concentrations of Ro 31-8220. Staurosporine, 1 microM, similarly potentiated the response to 100 microM histamine in 3 out of 4 experiments. KN-62 (10 microM) did not stimulate histamine-induced [3H]-IP1 accumulation. 8. In HEPES buffer to which no Ca2+ had been added, histamine stimulated a transient 451+/-107 nM increase in [Ca2+]i. Pretreatment with 1 microM and 10 microM Ro 31-8220 did not significantly alter the initial peak response to histamine, but slowed the rate at which histamine-induced increases in [Ca2+]i were returned to prestimulated levels. Pretreatment with KN-62 had no significant effect on the response to histamine, but consistently inhibited the secondary slower phase of the decline in [Ca2+]i. H-89 did not alter the histamine response. 9. The effect of histamine in stimulating Ca2+ extrusion was not confined to U373 MG cells, since 100 microM histamine also caused a rapid decrease in steady-state levels of [Ca2+]i in thapsigargin-treated human HeLa cells. 10. The results indicate that agonists which increase [Ca2+]i via activation of phosphoinositide metabolism can also stimulate a homeostatic mechanism which acts to reduce [Ca2+]i. The balance of the evidence indicates that in U373 MG cells the latter effect most likely involves a PKC-mediated stimulation of a Ca2+-extrusion pump.
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PMID:Dual effects of histamine and substance P on intracellular calcium levels in human U373 MG astrocytoma cells: role of protein kinase C. 950 96

Histamine (60 microM) produced ATP release from segments of guinea-pig vas deferens which was blocked by pyrilamine and triprolidine, H1-blockers, but not by ranitidine, an H2-blocker. The evoked-release was inhibited by the mitochondrial inhibitors, carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and oligomycin. Bradykinin (BK) and substance P (SP) also caused substantial and moderate release of ATP, respectively. The BK-evoked release of ATP was inhibited by HOE140, a B2-antagonist, but not by [Des-Arg10] HOE140, a B1-antagonist. On the other hand, VIP, angiotensin II (AII) and cholecystokinin-octapeptide (CCK-8) failed to elicit a measurable release of ATP. Histamine and BK also enhanced the release of ATP from superfused cultured smooth muscle cells. These results suggest that ATP may be released as an autacoid from the smooth muscles in the presence of these chemical mediators.
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PMID:ATP release caused by bradykinin, substance P and histamine from intact and cultured smooth muscles of guinea-pig vas deferens. 955 Feb 94

Primary cultures of human bronchial epithelial cells (HBE-cells) were established to measure granulocyte-macrophage colony stimulating factor (GM-CSF) release. HBE-cells showed a basal GM-CSF release (82+/-20 ng/well/24 h; 30 donors), which was increased by interleukin-1 beta(IL-1beta, 1 ng/ml) by 270%. This effect was blocked by 1 microM dactinomycin or 10 microM cycloheximide, i.e. the stimulatory effect of IL-1beta depended on de-novo synthesis. Histamine (100 microM) and acetylcholine ( 100 nM) stimulated GM-CSF release more than two-fold above the baseline. Nicotine (1 microM) increased GM-CSF release to a similar extent, and this effect was prevented by 30 microM (+)-tubocurarine. The stimulatory effect was attenuated or even lost with high agonist concentrations (10 microM acetylcholine; 100 microM nicotine) suggesting receptor desensitization. The muscarinic receptor agonist oxotremorine did not affect GM-CSF release. Serotonin, substance P and calcitonin-gene related peptide had no effect on GM-CSF release. In conclusion, acetylcholine can trigger GM-CSF release from human airway epithelial cells via stimulation of nicotinic receptors.
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PMID:Acetylcholine and nicotine stimulate the release of granulocyte-macrophage colony stimulating factor from cultured human bronchial epithelial cells. 960 35

1. The role of tachykinin NK1 receptors in the recruitment of eosinophils to airway nerves, loss of inhibitory neuronal M2 muscarinic receptor function and the development of vagal hyperreactivity was tested in antigen-challenged guinea-pigs. 2. In anaesthetized guinea-pigs, the muscarinic agonist, pilocarpine (1-100 microg kg(-1), i.v.), inhibited vagally induced bronchoconstriction, in control, but not in antigen-challenged guinea-pigs 24 h after antigen challenge. This indicates normal function of neuronal M2 muscarinic receptors in controls and loss of neuronal M2 receptor function in challenged guinea-pigs. Pretreatment of sensitized guinea-pigs with the NK1 receptor antagonists CP99994 (4 mg kg(-1), i.p.), SR140333 (1 mg kg(-1), s.c.) or CP96345 (15 mg kg(-1), i.p.) before antigen challenge, prevented M2 receptor dysfunction. 3. Neither administration of the NK1 antagonists after antigen challenge, nor pretreatment with an NK2 receptor antagonist, MEN10376 (5 micromol kg(-1), i.p.), before antigen challenge, prevented M2 receptor dysfunction. 4. Electrical stimulation of the vagus nerves caused a frequency-dependent (2-15 Hz, 10 V, 0.2 ms for 5 s) bronchoconstriction that was significantly increased following antigen challenge. Pretreatment with the NK1 receptor antagonists CP99994 or SR140333 before challenge prevented this increase. 5. Histamine (1-20 nmol kg(-1), i.v.) caused a dose-dependent bronchoconstriction, which was vagally mediated, and was significantly increased in antigen challenged guinea-pigs compared to controls. Pretreatment of sensitized animals with CP99994 before challenge prevented the increase in histamine-induced reactivity. 6. Bronchoalveolar lavage and histological studies showed that after antigen challenge significant numbers of eosinophils accumulated in the airways and around airway nerves. This eosinophilia was not altered by pretreatment with the NK1 receptor antagonist CP99994. 7. These data indicate that pretreatment of antigen-sensitized guinea-pigs with NK1, but not with NK2 receptor antagonists before antigen challenge prevented the development of hyperreactivity by protecting neuronal M2 receptor function. NK1 receptor antagonists do not inhibit eosinophil accumulation around airway nerves.
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PMID:Effects of tachykinin NK1 receptor antagonists on vagal hyperreactivity and neuronal M2 muscarinic receptor function in antigen challenged guinea-pigs. 964 42

Little is known about how the vascular reactivity of the coronary microcirculation is affected by upstream atherosclerotic disease. We have examined, with a wire myograph, the responses of intramyocardial arteries from hearts in which the epicardial vessels were either free of atherosclerotic lesions (non-diseased group) or were affected by atherosclerosis (diseased group). Vasodilator responses of preconstricted vessels to substance P (84.1 +/- 12.6 compared to 42.0 +/- 19.7%) were less in vessels from the diseased group (p < 0.05). In contrast, the relaxation to bradykinin (70.2 +/- 21.2 compared to 100.6 +/- 7.9%) was increased in vessels from the diseased group (p < 0.05). The dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium nitroprusside showed no significant differences between arteries from each group. 5-Hydroxytryptamine was without any significant vasodilator effect in arteries from either group. Assessment of contractile function revealed that the responses to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-N(G)-monomethylarginine in each group were not significantly different. Histamine, noradrenaline and dopamine were without any significant contractile response. These results demonstrate that upstream atherosclerosis does not confer any global impairment of endothelium-dependent vasorelaxant responses or smooth muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the myocardium.
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PMID:Reactivity of small intramyocardial arteries from atherosclerotic and non-atherosclerotic human hearts. 964 31

Rats are increasingly used to study airway inflammation and bronchial responsiveness. Relative little is known on the contribution of small airways in this animal model. We therefore compared the responsiveness to various inflammatory agents of isolated trachea, main bronchi (using classic organ bath) and isolated bronchioles (using small myograph) from Wistar and Fisher 344 rats. The largest contraction was elicited on all preparations by carbachol. Histamine elicited a (small) contraction only on bronchioles. The contractions elicited by serotonin, bradykinin, and the thromboxane A2-mimetic U-46619 were always relatively larger in bronchioles than in trachea and main bronchi. The sensitivities to carbachol and serotonin were smaller in bronchioles. The tachykinins substance P and neurokinin A elicited no substantial contraction on bronchioles or main bronchi. Trachea of Fisher 344 but not of Wistar rats showed a small contraction. No other differences were found between preparations from Wistar and Fisher 344 rats. It is concluded that rat trachea, main bronchi and small bronchioles show regional and strain-dependent variations in their responsiveness to contractile agents.
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PMID:Regionally different influence of contractile agonists on isolated rat airway segments. 971 2


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