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)

Whereas serotonin and substance P stimulate in-vivo and in-vitro myoelectric activity in the small intestine, their effects on transit are unclear. We used a validated in-vivo transit model in the chloral hydrate-anaesthetized rat to study the effects of serotonin, substance P and motilin, three putative mediators of carcinoid diarrhoea, on transit through the upper digestive tract. Intra-arterial serotonin accelerated gastric emptying of a radiolabelled liquid, while motilin accelerated overall upper gastrointestinal transit. Substance P slowed overall upper gastrointestinal transit without altering gastric emptying. The antagonists to serotonin receptor subtypes, R-zacopride (5-HT3) and ketanserin (5-HT2), also accelerated rat gastric emptying of liquids; in contrast, a 5-HT4 agonist, SC53116, resulted in a less pronounced effect on gastric emptying at the dose tested. We conclude that circulating substance P is unlikely to be an important accelerator of transit through the upper digestive tract; in contrast, hyperserotoninaemia significantly accelerates transit through the stomach, and 5-HT2 and 5-HT3 receptor subtypes may play a role in the motor effects of serotonin in the stomach.
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PMID:Effect of putative carcinoid mediators on gastric and small bowel transit in rats and the role of 5-HT receptors. 767 34

This investigation, conducted on 35 patients with advanced-stage gastric cancer, included 28 men and 7 women with a mean age of 50.1 years; also studied were 33 normal subjects as controls: 26 men and 7 women with a mean age of 45.8 years. Samples of blood and gastric juice were collected at fasting and in gastroscopy respectively. Substance P (SP), beta-endorphin (beta-EP), vasoactive intestinal peptide (VIP), motilin (MTL), gastrin (GT), and leu-enkephalin (LEK) of the sera and gastric juices were measured by radioimmunoassay kits. In the patients, SP and beta-EP of serum and gastric juice, and VIP, MTL and LEK of gastric juice, were higher than in the normal subjects (p < 0.01); gastrin of serum and gastric juice were decreased (p < 0.01). Serum and gastric juice SP, beta-EP levels correlated negatively with the gastrin (r = 0.462-0.519, p < 0.05). These data support the assumption that study of the peptides of serum and gastric juice can show a clinically significant change in gastric cancer patients.
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PMID:[Study on the peptides of serum and gastric juice in patients with gastric cancer]. 768 17

The pharmacological properties of the cyclic peptide Phe-cyclo[Lys-Tyr(3-tBu)-beta Ala-].trifluoroacetate (GM-109), a selective motilin antagonist, were investigated in the smooth muscle of the rabbit small intestine. GM-109 (0.1-3 microM) competitively inhibited contractions induced by porcine motilin (pMTL) in rabbit isolated duodenum longitudinal strips, with a pA2 value of 7.37 +/- 0.24. However, the contractile response to acetylcholine, to substance P, to prostaglandin F2 alpha and to KCl was unaffected by 10 microM GM-109 in the same preparation. Both GM-109 and pMTL competitively inhibited 125I-pMTL binding to motilin receptors in a homogenate of the rabbit small intestinal smooth muscle tissue. The pKi value of GM-109 and the pKd value of unlabeled pMTL were 7.99 +/- 0.04 and 9.25 +/- 0.06 (each n = 5), respectively. These results indicate that GM-109 is a selective and competitive motilin receptor antagonist in the smooth muscle of the rabbit small intestine. Thus this compound may be a useful pharmacological tool for examining the functional role(s) of motilin.
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PMID:GM-109: a novel, selective motilin receptor antagonist in the smooth muscle of the rabbit small intestine. 775 63

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.
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PMID:Possible action of human placental aminopeptidase N in feto-placental unit. 790 13

To evaluate the utility of screening for multiple gastrointestinal peptides in the evaluation of patients with chronic diarrhea, we studied 193 patients referred for evaluation of chronic diarrhea and eight patients with known peptide-secreting tumors as a reference group. Fasting plasma samples were assayed for motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, vasoactive intestinal polypeptide, gastrin-releasing peptide, and calcitonin during a protocol evaluation for causes of chronic diarrhea. Although none of the referred patients were found to have tumors, abnormal levels of one or more peptides were found in 86 of 193 patients (45%). Abnormal plasma peptide levels were sometimes as high in these patients as in patients with known peptide-secreting tumors and would have led to mistaken diagnoses of tumors much more often than they would have led to correct diagnoses. The positive predictive value of elevation of any assayed peptide was < 2% at realistic prevalence rates for peptide-secreting tumors; the negative predictive value of a series of normal results was > 99%, but much of this was due to the rarity of these tumors. Patients with chronic diarrhea should not be screened routinely with a panel of plasma peptide assays in an effort to detect tumors; instead, peptide levels should be ordered selectively. Elevated fasting concentrations of the plasma peptides measured in this study are most likely epiphenomena due to diarrhea and should not be the sole basis for invasive diagnostic or surgical management of these patients.
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PMID:Diagnostic value of fasting plasma peptide concentrations in patients with chronic diarrhea. 792 45

Hemodynamic stability is better preserved during bicarbonate hemodialysis compared to acetate. We have studied the effects of bicarbonate (HDB) and acetate hemodialysis (HDA) on plasma levels of vasoactive substances. The treatments were performed for 270 min. A cuprophan plate dialyzer was used. The ultrafiltration volume and the ultrafiltration rate were identical in the individual patients during the two treatments. In the case of vasoconstrictors there was an increase in neuropeptide Y (NPY) (20%, p < 0.01) during HDB and arginine vasopressin (AVP) was unchanged. Unlike this was the response during HDA when there was no change in NPY and a decrease in AVP (38%, p < 0.01). An increase in noradrenaline (NA) (41%, p < 0.05) occurred during HDA different from what was the case during HDB. There was a gradual increase in renin (PRA) during both HDB (141%, p < 0.05) and HDA (148%, p < 0.01). With respect to vasodilators there were no differences between the two regimes regarding calcitonin gene-related peptide (CGRP) and motilin (MOT). The change in substance P (SP) during the treatments was also similar but somewhat more pronounced during HDB. Thus, an initial rise occurred (HDB, 81%, p < 0.01; HDA, 36%, p < 0.05) followed by a decrease (HDB, 26%, p < 0.05) or a tendency to decrease (HDA, 12%, p = 0.058) during the remaining part of the treatment. A rise in beta-endorphin (beta-END) occurred during HDB (10%, p < 0.05) but not during HDA. An increase in vasoactive intestinal peptide (VIP) occurred during HDB (27%, p < 0.05) different from the decrease during HDA (11%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis. 800 26

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

Nineteen different antisera raised against mammalian hormones were used to identify the occurrence and distribution of endocrine cells in the gut of grass carp (Ctenopharyngodon idellus). Positive reactions were obtained in gut epithelium with antisera gastrin, glucagon, gastric inhibitory peptide, leucine enkephalin, substance P, and bovine pancreatic polypeptide. No immunoreactive product was formed using antisera against somatostatin, 5-hydroxytryptamine, insulin, avian pancreatic polypeptide, motilin, cholecystokinin, secretin, neurotensin, vasoactive intestinal polypeptide, bombesin, neuron-specific enolase, prochymosin, and pepsinogen. The exact distribution mapping of six kinds of immunoreactive endocrine cells throughout the gut of grass carp (C. idellus) is presented. The morphological characteristics of immunoreactive endocrine cells is described. Their distribution characteristics and possible modes of secretion and function are discussed. Finally, the possible relationship between the transplantation of these cells in the gastro-entero-pancreatic endocrine system is discussed.
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PMID:An immunocytochemical study of endocrine cells in the gut of a stomachless teleost fish, grass carp, Cyprinidae. 816 83

Studies on the physiological role of motilin, and more recently, on the relationship between motilin and erythromycin A, have been hampered by the lack of antagonists. We now have discovered such a compound. ANQ-11125 displaces motilin bound to an homogenate of rabbit antral smooth muscle tissue. The dissociation constant (pKd) was 8.16 +/- 0.10. However, ANQ-11125 did not induce contractions of segments of rabbit duodenum, except at high concentrations. In the presence of 1 microM ANQ-11125 the dose response curves of erythromycin-A, De(N-methyl)-N-ethyl-8,9 anhydroerythromycin A 6,9-hemiacetal and motilin were shifted about one log unit to the right, but the responses to ACh and Substance P were unaffected. Schild-analysis showed the competitive nature of the interaction and allowed the calculation of the pA2: 7.03 +/- 0.05 (motilin curves) and 7.55 +/- 0.06 (EM-523 curves). This is the first report of a motilin antagonist. Its properties definitively prove that motilides are motilin agonists.
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PMID:The motilin antagonist ANQ-11125 blocks motilide-induced contractions in vitro in the rabbit. 829 50

During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis.
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PMID:Changes in plasma levels of vasoactive peptides during standard bicarbonate hemodialysis. 844 68


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