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)

This study explored the modulatory effects of nitric oxide and thromboxane A2 on contractions to ergonovine and methylergonovine in human coronary arteries. To elucidate the different role of nitric oxide synthase in the response to the ergot alkaloids, the serotonin (5-HT) receptors involved in nitric oxide synthase in the response to the ergot alkaloids, the 5-HT receptors involved in nitric oxide release and the contraction of the vascular smooth muscle were characterized with more selective 5-HT-receptor agonists and antagonists. Rings of human coronary arteries from explanted hearts were suspended in organ chambers for isometric tension recording. After testing for contractile (potassium chloride, 60 mM) and endothelial function (substance P, 10(-8) M), respectively, they were exposed to ergot alkaloids or other agonists in the absence or presence of U 46619 (10(-9) M), or nitro-L-arginine (10(-4) M), or both. Ergonovine and methylergonovine were comparable, weak vasoconstrictors in untreated preparations. Contractions to ergonovine were augmented by U 46619, but not by nitro-L-arginine. Contractions to methylergonovine were augmented only by combining U 46619 and nitro-L-arginine. Serotonin and methylergonovine, but not ergonovine, elicited endothelium-dependent, nitric oxide-mediated relaxations. Nonselective 5-HT(1B/1D)-receptor stimulation caused both contractions and relaxations; selective 5-HT1B stimulation caused relaxations only. In the human coronary artery, contractions to ergonovine are not dependent on NO release but are synergistically augmented by thromboxane. Methylergonovine causes similar effects on the vascular smooth muscle, but contractions are inhibited by the release of NO from the endothelium. The 5-HT receptor on the endothelium appears to be different from the receptor on the vascular smooth muscle, which mediates the contractile response to the ergot alkaloids.
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PMID:Modulation of contractions to ergonovine and methylergonovine by nitric oxide and thromboxane A2 in the human coronary artery. 1106 24

Acute diarrhoea continues to carry a high morbidity and mortality worldwide. Intestinal infection is the major cause of acute diarrhoea although the prevalence of individual pathogens varies according to geographic location. In many countries in the industrialized world, reports of intestinal infections continue to increase; these are largely related to waterborne and foodborne outbreaks. Acute diarrhoea may be due to increased intestinal secretion, commonly as a result of infection with enterotoxin-producing organisms (enterotoxigenic Escherichia coli, Vibrio cholerae) or to decreased intestinal absorption from infection with organisms that damage the intestinal epithelium (enteropathogenic E. coli, Shigella sp., Salmonella sp.). Although oral rehydration therapy has reduced the mortality associated with acute diarrhoea, the diarrhoea attack rate remains unchanged and stool volume often increases during the rehydration process. The search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce stool volume has been going on for more than 20 years. Research during the past decade has highlighted the importance of neurohumoral mechanisms in the pathogenesis of diarrhoea, notably the role of 5-hydroxytryptamine, substance P, vasoactive intestinal polypeptide and neural reflexes within the enteric nervous system. Cholera toxin, E. coli enterotoxins and Clostridium difficile toxin A are known to invoke these mechanisms in diarrhoea pathogenesis. This new dimension of intestinal pathophysiology has already exposed possible novel targets for anti-secretory therapy, namely, 5-HT receptor antagonists, substance P antagonists and the possibility for potentiating the proabsorptive effects of endogenous enkephalins by use of enkephalinase inhibitors. There now seems to be a real possibility that anti-secretory therapy will become more widely available in the future.
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PMID:Novel targets for the pharmacotherapy of diarrhoea: a view for the millennium. 1110 Sep 92

By means of intracellular recordings from sympathetic ganglion in vitro, the present study was to investigate whether the receptors of substance P (SP) and 5-hydroxytryptamine (5-HT) exist in the same neuron or separately in different neurons of guinea pig celiac ganglion (CG) and inferior mesenteric ganglion (IMG) and whether there are some interactions between the two transmitters. Of the 133 neurons of CG, 66 (49.6%) responded to both SP and 5-HT, 40 (30.1%) only to SP or 5-HT, 27 (20.3%) insensitive to both. The corresponding numbers of the corresponding groups of neurons of the 129 IMG neurons are 47 (36.4%), 65 (50.4%) and 17 (13.2%). Continuous superfusion of IMG with 5-HT did not affect SP depolarization, while continuous superfusion of IMG with SP did not affect 5-HT depolarization. The results indicate that SP receptor and 5-HT receptor may exist in the same neuron, and neither affects each other.
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PMID:Substance P- and 5-hydroxytryptamine-mediated depolarization in sympathetic ganglion neurons. 1149 58

Capsaicin, the pungent component of hot peppers, and the venom of the spider Phoneutria nigriventer are able to activate sensory nerves resulting in cutaneous neurogenic plasma extravasation. This study was undertaken to compare the ability of these substances to evoke oedema in the rat hind-paw and mechanisms underlying this effect. Subplantar injection of either Phoneutria nigriventer venom (PNV; 1-100 microg/paw) or capsaicin (10-200 microg/paw) caused a significant paw oedema that was potentiated by CGRP (10 pmol/paw). In rats treated neonatally with capsaicin to deplete neuropeptides, the paw oedema induced by either PNV (100 microg/paw) or capsaicin (100 microg/paw) was partially reduced (P<0.05). The tachykinin NK1 receptor antagonist SR140333 (0.2 micromol/kg; i.v.) prevented the paw oedema induced by the tachykinin NK1 receptor agonist GR73632 (30 pmol/paw) and partially reduced paw oedema induced by PNV or capsaicin. Treatment of rats with compound 48/80 (5 mg/kg; s.c. 3 days) or with both H1 receptor antagonist (mepyramine; 1 nmol/paw) and 5-HT receptor antagonist (methysergide; 1 nmol/paw) significantly inhibited PNV- or capsaicin-induced paw oedema. The combined treatment with mepyramine and methysergide and SR140333 further reduced PNV- and capsaicin-induced paw oedema. The bradykinin B2 receptor antagonist Hoe 140 affected neither PNV- nor capsaicin-induced responses. Our results suggest that PNV and capsaicin each induce paw oedema that is partially mediated by activation of sensory fibers culminating in the release of substance P as well as by activation of mast cells which in turn release amines such as histamine and 5-HT.
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PMID:Comparative effect of Phoneutria nigriventer spider venom and capsaicin on the rat paw oedema. 1155 18

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.
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PMID:Regulation mechanisms of intestinal secretion: implications in nutrient absorption. 1198 1

Proteinase inhibitors from plants represent a form of storage protein or may be involved in plant defense mechanisms against pests and diseases. In this study, we have investigated the oedematogenic activity of DMTI (20 kDa) and DMTI-II (23 kDa), two serine proteinases inhibitors isolated from Dimorphandra mollis (Leguminosae-Mimosoideae) seeds, belonging to the Kunitz family. Paw oedema was induced in male Wistar rats, and measured before and selected times after injection of the proteinase inhibitors. Injection of DMTI-II (3-100 microg/paw) induced a dose-dependent rat paw oedema of rapid onset and short duration, whereas DMTI (3-100 microg/paw) caused a discrete response. The histamine/5-HT receptor antagonist cyproheptadine (2 mg/kg) markedly reduced the DMTI-II-induced oedema. The bradykinin B2 receptor antagonist JE 049 (0.6 mg/kg), the tachykinin NK1 receptor antagonist SR140333 (100 microg/kg) or the NK2 receptor antagonist SR48968 (1 mg/kg) all significantly reduced the DMTI-II-induced oedema. Depletion of sensory neuropeptides by capsaicin also resulted in a significant reduction of oedema formation. In rat isolated peritoneal mast cells, DMTI-II failed to directly release histamine. In conclusion, the proteinase inhibitor DMTI-II induces rat paw oedema by triggering the formation of different inflammatory mediators and pathways, where mast cells and sensory fibers seem to play a pivotal role.
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PMID:Oedematogenic activity induced by Kunitz-type inhibitors from Dimorphandra mollis seeds. 1638 83

This study provides a comprehensive evaluation of 5-HT(3) receptor functional distribution in both the rat and mouse intestinal tract. 5-HT(3A-S) receptor splice variant mRNA was expressed throughout the intestine of the rat and mouse; the 5-HT(3A-L) variant being more common in the rat.5-HT, m-CPB, 1-PBG and 2-methyl-5-hydroxytryptamine (2m5-HT) induced contraction in the jejunum, ileum, proximal colon and distal colon of the rat (pEC(50) range: 2m5-HT, 5.86+/-0.40 to m-CPB, 7.47+/-0.27) and mouse (pEC(50) range: 1-PBG, 5.34+/-0.06 to m-CPB, 6.49+/-0.14) in the presence of nontarget 5-HT receptor antagonists, methysergide (1 muM) and GR125487 (0.1 microM). The rank orders of potency in the four regions of the rat and mouse intestine were concordant with the accepted order and the responses to 5-HT were inhibited by ondansetron (0.1 microM).5-HT(3)-induced contractions to 5-HT were reduced by tetrodotoxin (1 microM). Pargyline (10 muM) and fluoxetine (1 microM) potentiated responses in the rat jejunum. Atropine (0.1 microM) potentiated 5-HT(3)-induced responses in the rat jejunum (E(max) 49-65%), but attenuated responses in most other regions of the rat and mouse (e.g. mouse ileum: E(max) 57-26%). In the rat jejunum, L-NAME (100 microM) mimicked the effect of atropine, hexamethonium (100 microM) suppressed 5-HT(3)-induced responses, but tachykinin receptor antagonists were without effect. It is concluded that functional 5-HT(3) receptors are present in nerves along the length of the rat and mouse intestinal tract. The mouse proximal colon was found to discriminate 5-HT(3) receptor agonist profiles better than any other region in the rat or mouse. The rat jejunum shows evidence of 5-HT uptake and inactivation processes as well as inhibitory nitrergic and nontachykinin excitatory pathways associated with the 5-HT(3)-induced response.
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PMID:Activation of 5-HT3 receptors in the rat and mouse intestinal tract: a comparative study. 1677 Mar 18

Despite the conserved function of aggression across taxa in obtaining critical resources such as food and mates, serotonin's (5-HT) modulatory role on aggressive behavior appears to be largely inhibitory for vertebrates but stimulatory for invertebrates. However, critical gaps exist in our knowledge of invertebrates that need to be addressed before definitively stating opposing roles for 5-HT and aggression. Specifically, the role of 5-HT receptor subtypes are largely unknown, as is the potential interactive role of 5-HT with other neurochemical systems known to play a critical role in aggression. Similarly, the influence of these systems in driving sex differences in aggressive behavior of invertebrates is not well understood. Here, we investigated these questions by employing complementary approaches in a novel invertebrate model of aggression, the stalk-eyed fly. A combination of altered social conditions, pharmacological manipulation and 5-HT2 receptor knockdown by siRNA revealed an inhibitory role of this receptor subtype on aggression. Additionally, we provide evidence for 5-HT2's involvement in regulating neuropeptide F activity, a suspected inhibitor of aggression. However, this function appears to be stage-specific, altering only the initiation stage of aggressive conflicts. Alternatively, pharmacologically increasing systemic concentrations of 5-HT significantly elevated the expression of the neuropeptide tachykinin, which did not affect contest initiation but instead promoted escalation via production of high intensity aggressive behaviors. Notably, these effects were limited solely to males, with female aggression and neuropeptide expression remaining unaltered by any manipulation that affected 5-HT. Together, these results demonstrate a more nuanced role for 5-HT in modulating aggression in invertebrates, revealing an important interactive role with neuropeptides that is more reminiscent of vertebrates. The sex-differences described here also provide valuable insight into the evolutionary contexts of this complex behavior.
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PMID:Sex differences in aggression: Differential roles of 5-HT2, neuropeptide F and tachykinin. 3069 38


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