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)

1. Mechanical activity was recorded in isolated muscle preparations from circular and longitudinal layers of gastric fundus, corpus and antrum and from the duodenum of pigs, using conventional organ bath technique. Rectangular current pulses were applied to the muscle strips for electrical field stimulation (EFS). 2. Fundic and circular corpus preparations developed a marked spontaneous tonic activity. Vasoactive intestinal polypeptide (VIP, 10(-9)-10(-7) mol l-1) inhibited this spontaneous activity. This inhibitory effect was not affected by application of tetrodotoxin (TTX) showing its myogenic nature. 3. Pretreatment of fundic and circular corpus preparations with VIP reduced the excitatory responses to substance P, bombesin, serotonin and histamine, but it had no effect on the acetylcholine (ACh)-induced tonic and phasic activity. 4. Longitudinal duodenal preparations showed purely phasic activity which was almost insensitive to VIP. In circular duodenal preparations particularly strong spontaneous tonic contractions were observed which could be inhibited by VIP. 5. Circular duodenal preparations excised 3-5 cm postpyloric had a spontaneous tone which could reach up to 80% of the maximum contractions induced by 10(-4) mol l-1 ACh. These preparations were chosen for further pharmacological studies and for experiments with EFS. VIP was the most powerful substance for the inhibition of spontaneous tone, followed by serotonin, PGE2 and bradykinin. This type of preparation exhibited particularly strong inhibitory effects to EFS; even single stimuli could induce near maximum relaxation. The inhibition induced by EFS was unaffected by treatment with ATP, guanethidine, atropine, methysergide and apamin. TTX completely abolished the EFS-induced relaxation, showing its neurogenic nature. 6. Porcine circular duodenum is a good model for studying the transmitter system of the non-adrenergic, non-cholinergic (NANC) innervation. The results are consistent with the assumption that VIP is the transmitter in this system, although the very slow time-course of the VIP-induced inhibition in comparison with the EFS-induced inhibition is not consistent with this notion.
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PMID:Responses of porcine gastric and duodenal smooth muscle to VIP. 172 15

Airway submucosal glands are by volume the most important source of macromolecules in airway secretions. These secretions, containing gel-forming mucins, antibacterial proteins, and antiproteases, comprise the major defensive barrier protecting the host against airborne pathogens. The identification of the mechanisms regulating secretion from the submucosal glands is key to understanding the genesis of this barrier and how it is altered by disease processes. Using a variety of methods, we and others have identified on the gland cells of several species receptors specific for ACh, norepinephrine, substance P, VIP, PGE1, PGE2, PGA1, PGD2, histamine and bradykinin. These receptors all participate in modulating the secretory activity of the airway submucosal glands. Studies of homogeneous cultures of bovine airway serous cells have yielded detailed information regarding the beta-adrenergic receptor on these cells. Using radioligand binding techniques, we found evidence for the presence of a single high affinity beta receptor of beta-2 subtype. Occupancy of this receptor by isoproterenol causes an elevation in the concentration of intracellular cAMP, which in turn stimulates the phosphorylation of a subset of cytoplasmic and membrane proteins. Based on the kinetics and pharmacology of these effects, it is likely that cAMP functions as a second messenger in the serous cell secretory pathway, probably acting through protein kinases. Current efforts are directed at identification of those phosphoproteins whose phosphorylation and dephosphorylation times are consistent with their possible roles in secretion.
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PMID:Receptors on airway gland cells. 215 62

We have previously shown that Entamoeba histolytica lysates contain the neurohormones serotonin, neurotensin, immunoreactive substance P, and probably acetylcholine, and that amebic lysates inhibit sodium and chloride absorption and stimulate chloride secretion in the rat descending colon as measured by the Ussing chamber-voltage clamp technique. We now demonstrate that these transport effects have both calcium-dependent and calcium-independent components. In addition, arachidonic acid metabolites of the cyclooxygenase pathway are probably involved in the Entamoeba histolytica-induced changes in colonic transport that are not dependent on Ca++ entry. Prostaglandin E2 (10(-5) M), indomethacin (10(-6) M), piroxicam (5 x 10(-5) M), and mepacrine (10(-4) M) partially inhibited the amebic lysate effect on active transport in the rat descending colon. In addition, verapamil (10(-4) M) partially inhibited the effect of amebic lysates. The effect of verapamil was additive with that of indomethacin, totally blocking the effect of amebic lysate on short-circuit current. However, amebic lysates do not contain prostaglandin E2 as measured by sensitive radioimmunoassay. Amebic lysates stimulated prostaglandin E2 release from rat colonic mucosal strips. Amebic lysate significantly increased colonic cyclic adenosine monophosphate content. Piroxicam inhibited the lysate-induced increase in colonic cyclic adenosine monophosphate content. These results indicate that although amebic lysate does not contain prostaglandin E2, it caused arachidonic acid metabolites to be produced by the cyclooxygenase pathway, and these are probably involved in the Entamoeba histolytica-induced changes in colonic transport. Neurohormones in Entamoeba histolytica may act directly on colonic tissue to stimulate intestinal secretion, probably via a Ca+(+)-dependent mechanism that is blockable by verapamil, or indirectly via stimulation of prostaglandin E2 generation and release from the rat colon via a cyclic adenosine monophosphate-dependent mechanism. These effects appear separate. The cyclic adenosine monophosphate-dependent secretion is the predominant mechanism in this model of colonic amebic diarrhea.
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PMID:Role of prostaglandins and calcium in the effects of Entamoeba histolytica on colonic electrolyte transport. 222 9

The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways.
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PMID:Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice. 232 44

1. An epithelium-derived inhibitory factor (EpDIF) released by guinea-pig tracheal epithelium was evaluated in a co-axial bioassay system consisting of an epithelium-intact guinea-pig tracheal tube surrounding endothelium-denuded rat aortic strip. 2. Histamine and several muscarinic agonists induced concentration-dependent relaxation of phenylephrine-contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea-pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 microM), 1,1-dimethyl-4-phenylpiperazinium (DMPP) (25 microM), calcium ionophore A23187 (0.5 microM), bradykinin (0.05-0.5 microM), substance P (5 microM), platelet activating factor (PAF, 1-100 nM), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1-10 nM) as well as hyperosmotic stimuli. 3. Prostaglandin E2 (PGE2) induced concentration-dependent contraction of endothelium-denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 microM) the cyclo-oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P-450 inhibitors metyrapone (1 mM) and SKF 525A (25 microM). This suggests that EpDIF is neither a prostanoid nor a cytochrome P-450 metabolite of arachidonic acid. 4. The soluble guanylate cyclase inhibitor, methylene blue (50 microM), caused small but significant increases in the potencies of both histamine and methacholine in co-axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The beta-adrenoceptor antagonist, (-)-propranolol (1 microM), and the PAF-receptor antagonist, WEB 2086 (50 microM), also failed to alter significantly EpDIF-modulated relaxations. These data suggest that EpDIF is neither a stimulant of fiadrenoceptors nor of PAF receptors. 5. The present study provides some evidence that this vascular smooth muscle-sensitive EpDIF may not be related to the putative EpDIF previously hypothesized to modulate directly spasmogen-induced airway smooth muscle tone.
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PMID:Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF). 239 Jun 83

The relationship between desensitization of iris muscarinic acetylcholine receptors and the receptor-mediated phosphoinositide hydrolysis system was examined in rabbit eyes. Rabbits were treated topically in one eye, the other eye served as control, with 2% pilocarpine in three successive doses (2 X 50 microL) at 32, 24 and 6 hr prior to sacrifice. The polyphosphoinositide (PPI) response was measured in vitro in the iris both as loss of 32P-radioactivity from phosphatidylinositol 4,5-bisphosphate (PIP2) and as accumulation of myo-[3H]-inositol trisphosphate (IP3); arachidonic acid (AA) liberation was measured by radiochromatography; prostaglandin (PG) E2 release was measured by radiochromatography and radioimmunoassay; and myosin light chain (MLC) phosphorylation was measured with SDS-polyacrylamide gel electrophoresis. Desensitized tissues showed significant decreases in carbachol-induced PIP2 hydrolysis, IP3 accumulation, AA liberation, PGE2 synthesis and muscle contraction. These effects are specific to cholinergic receptors in the iris, since substance P-induced IP3 accumulation and PGE2 release, was not affected by the cholinergic desensitization. The cholinergic desensitization of the PPI response in the iris is reversible. These findings are in accord with our previous studies on alpha 1-adrenergic desensitization of the PPI response in this tissue, and they add further support to the hypothesis that changes in the activities of the receptor-mediated phosphoinositide hydrolysis system and its derived second messengers may underlie the mechanism of alpha 1-adrenergic and muscarinic cholinergic subsensitivity in the iris-ciliary body.
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PMID:Muscarinic cholinergic induced subsensitivity in rabbit iris-ciliary body. Effects on myo-inositol triphosphate accumulation, arachidonate release, prostaglandin synthesis, and contraction. 244 62

Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint.
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PMID:Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in response to bradykinin. 247 45

The relationship between glucose metabolism and cyclic-AMP production in dental pulp in the presence of chemical mediators was investigated in vitro. It is generally accepted that oxidation of glucose-6-14C is indicative of metabolism by the glycolytic pathway whereas that of glucose-1-14C occurs by the hexose monophosphate shunt. The 14CO2 productions from both routes were compared in dental pulp from cattle and rats in the presence of each of several chemical mediators: bradykinin (1.7-3.3 micrograms/ml), prostaglandin E1 (0.3 micrograms/ml), prostaglandin E2 (0.3 micrograms/ml), histamine (33 micrograms/ml), and 5-hydroxytryptamine (33 micrograms/ml). The effects of dental filling materials on glucose oxidation, and cyclic-AMP production by chemical mediators in pulp tissues were also investigated. The results obtained were as follows: 1) Glucose oxidation in dental pulp was stimulated by chemical mediators generally by way of the Embden-Meyerhof Parnas pathway, and was further stimulated by the medium containing bradykinin. However, it was depressed in the presence of higher concentrations of chemical mediators, especially depressed in the HMS pathway. 2) The oxidation ratio of glucose-1-14C to glucose-6-14C (G1/G6) in dental pulp was 4 to 8 in the cattle and 0.6 in the rat, showing clear differences in glucose oxidation between the two animals. 3) Moreover, glucose oxidation in rat dental pulp was 60 to 80 times higher in the EMP pathway and 5 to 10 times higher in the HMS pathway than those in the cattle. 4) Dental filling materials such as silicate cement, zinc phosphate cement, calcium hydroxide, and eugenol cement severely depressed glucose-6-14C oxidation in bovine dental pulp when used at high concentrations, but not at low concentrations. 5) The chemical mediators tested in this experiment (PGE1, PGE2, histamine, 5-HT, bradykinin, and substance P) stimulated cyclic AMP production in rat dental pulp. The production was highest with PGE1 and PGE2. The cyclic AMP production was further stimulated by addition of histamine or 5-HT to the medium containing PGE1 or PGE2.
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PMID:[Studies on the relation between glucose metabolism and c-AMP formation in dental pulps in the presence of inflammatory chemical mediators in vitro]. 256 77

The pronounced synovial hyperplasia often found in the joints of patients with rheumatoid arthritis could be explained partially by the action of monocyte-macrophage polypeptides (monokines). This report demonstrates that two cytokines which may be derived from monocyte-macrophage populations, namely platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), stimulate the DNA synthesis and proliferation of human synovial fibroblast-like cells cultured in low (i.e., 1%) fetal bovine serum. Epidermal growth factor, insulin-like growth factor-I, insulin-like growth factor-II (multiplication stimulating activity) and substance P were inactive. Unlike IL-1, PDGF and FGF do not also stimulate PGE2, plasminogen activator, and hyaluronic acid levels. Thus PDGF and FGF, arising from stimulated monocyte-macrophages, may play a role in the stimulation of mesenchymal cell proliferation that often accompanies chronic inflammatory arthritic disease. The synovial cells respond to a variety of cytokines in different ways suggesting multiple-signaling pathways.
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PMID:Stimulation of human synovial fibroblast DNA synthesis by platelet-derived growth factor and fibroblast growth factor. Differences to the activation by IL-1. 270 21

Watery diarrhoea as distinct from dysentery is occasionally seen in intestinal amoebiasis, suggesting a component of intestinal secretion. To study the pathogenesis of this watery diarrhoea, we evaluated the effect of lysates of Entamoeba histolytica on active intestinal electrolyte transport using rabbit ileum and rat colon studied by the Ussing chamber-voltage clamp technique. Amoebic lysates added to the ileal and colonic mucosal surfaces did not alter electrolyte transport; in contrast, addition to the ideal and colonic serosal surfaces caused an increase in short-circuit current which was transient in the ileum but more prolonged in the colon. This increase in current corresponded to inhibition of active Na+ and Cl- absorption and apparent stimulation of Cl- secretion in rat colon. In rabbit ileum, the short-circuit current response was: (1) dependent on serosal Ca2+, (2) inhibited by serosally applied verapamil, (3) associated with reversible desensitization, and (4) only partially inhibited by heating. These characteristics were similar to those of a series of neurohumoral substances present in mammalian intestinal mucosa which affect active electrolyte transport by increasing the permeability of the basolateral membrane to Ca2+. Substances with these properties identified include serotonin, substance P and neurotensin. All three substances were shown to be present in amoebic lysates by radioimmunoassay. Serotonin was also present by high performance liquid chromatography (HPLC) and thin layer chromatography, and neurotensin by HPLC. Prostaglandins were not present by radioimmunoassay. Attempts were made to determine which of these neurohumoral substances contributed to the changes in intestinal transport caused by amoebic lysates. Serotonin was thought to be involved, from the inhibition of the transport effect of amoebic lysate on rat colon by anti-serotonin antibody and by bufotenine, which inhibits the effect of serotonin on ion transport. Prostaglandins also appeared to be involved, since pretreatment with PGE2 or indomethacin inhibited the effects of amoebic lysate on transport. We conclude that amoebae contain neurohumoral substances, including serotonin, neurotensin and substance P, which may be important in the intestinal secretion caused by amoebae. Serotonin appears partially responsible for the intestinal secretion. In addition, amoebae may induce prostaglandin synthesis by the intestinal mucosa which could also contribute to the secretory response. The relation between the neurohumoral substances which act by Ca2+ and the prostaglandins presumably caused to be synthesized in the intestinal mucosa is not known.
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PMID:Secretory hormones of Entamoeba histolytica. 286 Oct 68


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