Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotensin (NT) and bombesin, which are heterogeneously distributed in both brain and gastrointestinal tissue of several mammalian species, inhibit the formation of stress-induced gastric ulcers in rats. Many other endogeneous neuropeptides have also been reported to be present in brain and gastrointestinal tissue. The present study was conducted to evaluate the effect of some of these peptides on the development of cold-restraint stress (CRS)-induced gastric ulcers in rats. In addition, the effect of thyrotropin-releasing hormone (TRH), which antagonizes many of the CNS effects of NT, was investigated to determine whether this tripeptide antagonizes the cytoprotective effect of NT in this CRS model. All peptides were initially administered intracisternally (ic) in doses equimolar to 30 micrograms NT. As previously reported, NT (30 micrograms, ic) completely prevented the development of gastric ulcers in rats exposed to three hours of CRS. Bombesin, beta-endorphin, substance P, and somatostatin also exhibited cytoprotective activity. Several other peptides studied in the CRS model exerted no significant effects on the development of gastric ulcers; these included cholecystokinin octapeptide, gastrin, leu-enkephalin, met-enkephalin, and bradykinin. Two peptides, vasoactive intestinal polypeptide and TRH, significantly increased the severity of gastric ulcerations. The cytoprotective effect of NT was dose dependent. In contrast, lower doses of beta-endorphin, substance P, and somatostatin were cytoprotective whereas higher doses were not. Finally, concomitant ic injections of TRH antagonized the cytoprotective effects of NT and bombesin, but not that of beta-endorphin. The present results suggest that certain brain peptides may participate in modulating the gastric mucosal barrier, thereby increasing or decreasing its vulnerability to stress-induced lesions.
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PMID:The effect of centrally administered neuropeptides on the development of stress-induced gastric ulcers in rats. 630 95

A porcine kidney microsomal metalloendopeptidase has been enriched 3900-fold. Gel filtration on a calibrated Toyo-Soda G-3000 SW column indicated an appropriate molecular weight for the endopeptidase of 88,000 +/- 2000. The purified enzyme is inhibited by a number of synthetic inhibitors of thermolysin. The endopeptidase hydrolyzes the succinyl (Suc)-containing fluorogenic peptide substrate Suc-Ala-Ala-Phe-(7-amino-4-methylcoumarin) at the Ala-Phe position with a Km of 2.9 X 10(-4) M. The endopeptidase also hydrolyzes a variety of peptides including corticotropin, substance P, angiotensin I and II, neurotensin, somatostatin, bradykinin, and the renin tetradecapeptide substrate. The endopeptidase hydrolyzes both [Leu]- and [Met]enkephalin at the Gly-Phe bond.
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PMID:Purification of a membrane-bound metalloendopeptidase from porcine kidney that degrades peptide hormones. 703 58

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

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

Intra-adrenal factors promote basal as well as adrenocorticotropic hormone (ACTH)-, angiotensin-, and flow-induced steroid secretion. Because endothelial cells respond to changes in flow and are in a close anatomical relationship to steroidogenic cells, we examined the effect of endothelial cells on the secretion of aldosterone from zona glomerulosa (ZG) cells. Endothelial cells and endothelial cell-conditioned medium (EC-CM) stimulated the release of aldosterone from ZG cells. The stimulatory effect was related to the concentration of endothelial cells or EC-CM. The maximal stimulatory effect was 60-70% of the maximal effect of ACTH. Endothelial cells alone did not produce aldosterone. Human fibroblasts were ineffective in promoting aldosterone release. Endothelial cells and EC-CM failed to stimulate cortisol release from zona fasciculata cells. Treatment of the EC-CM with trypsin and pronase abolished the activity, indicating that a protein mediated the effect. However, the EC-CM activity could be distinguished from angiotensin, endothelin-1, and bradykinin. The factor stimulated the formation of pregnenolone but not the conversion of corticosterone to aldosterone. This endothelium-derived steroidogenic factor appeared to be a novel stimulus to aldosterone secretion. This study represents the first demonstration that endothelial cells alter endocrine function in vitro.
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PMID:Endothelial cells stimulate aldosterone release from bovine adrenal zona glomerulosa cells. 830 36

Group B streptococci were recently reported to possess a cell-associated collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly purified enzyme nor crude group B streptococcal cell lysate solubilized a film of reconstituted rat tail collagen, an activity regarded as obligatory for a true collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced amino acid sequence showed 66.4% identity to the PepF oligopeptidase from Lactococcus lactis, a member of the M3 or thimet family of zinc metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase activity and degraded a variety of small bioactive peptides, including bradykinin, neurotensin, and peptide fragments of substance P and adrenocorticotropin.
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PMID:Characterization of PepB, a group B streptococcal oligopeptidase. 875 83

A neutral endopeptidase (NEP) from Lactococcus lactis has recently been cloned and shown to contain high sequence homology with the human neutral endopeptidase, endopeptidase 24.11 (I. Mierau et al., J. Bacteriol. 175, 2087-2096, 1993). The gene for the neutral endopeptidase from L. lactis was cloned into the pQE expression vector, resulting in the fusion of a hexahistidine at the N-terminus. The recombinant enzyme was expressed to high levels in Escherichia coli (approximately 10 mg/liter of culture) and purified to homogeneity in a two-step procedure. A number of peptides were studied as substrates for the enzyme. The enzyme cleaves the following peptides at the Gly3-Phe4 bond: enkephalins, dynorphins A-6, A-8, A-9, A-10, A-13, and A-17, and alpha-neo-endorphin. In addition the enzyme hydrolyzes bradykinin, substance P, beta-endorphin, ACTH, and VIP. Although the cleavage patterns observed are similar to that seen with mammalian neutral endopeptidase, the lactococcal enzyme more efficiently cleaves larger peptide substrates. As observed with the mammalian neutral endopeptidase, the lactococcal enzyme exhibits higher kcat/K(m) values for the enkephalins than for their corresponding amides, indicating the functionality of an active-site arginine. Inactivation of the lactococcal endopeptidase by diethyl pyrocarbonate and protection afforded by the substrate dynorphin A-6 indicate the functionality of a positionally conserved active-site histidine. This was confirmed by demonstrating that conversion of this histidine, histidine 587, to glutamine generated inactive enzyme. Similarly, conversion of the putative zinc ligand glutamate 535 to glutamine led to inactive enzyme. These studies indicate a conservation of critical catalytic residues between the two enzymes and suggest that the lactococcal endopeptidase is a better model than thermolysin for the mammalian enzyme.
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PMID:Heterologous expression and characterization of recombinant Lactococcus lactis neutral endopeptidase (neprilysin). 880 62

Bradykinin and beta-endorphin increases during acute pancreatitis are thought to contribute to the development of hypotension and myocardial depression in acute pancreatitis. beta-Endorphin release is mediated by trypsin-like enzymes and bradykinin from the pituitary gland. This study was undertaken to investigate the effect of a long-acting bradykinin receptor antagonist on bradykinin and beta-endorphin release and on hemodynamic changes during acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligation of the accessory duct. Serum bradykinin and plasma beta-endorphin levels and cardiovascular function were measured. Twelve dogs (control group) were given 10 ml/kg/h of lactate Ringer's solution intravenously beginning 1 h before the induction of pancreatitis and continuing throughout the experiments. Six dogs received an intravenous infusion of 0.6 mg/kg/h of a new bradykinin receptor antagonist, HOE 140, D-Arg-[Hyp3, Thi5, D-Tic, Oic8]-bradykinin, in lactate Ringer's solution soon after the induction of pancreatitis. Six of twelve dogs in the control group, and none of the six dogs in the bradykinin receptor antagonist group, died during the experiments. Serum bradykinin levels in both groups increased until 1 h after the induction of pancreatitis, but thereafter the levels in the bradykinin receptor antagonist group decreased gradually until 5 h after induction, and levels were significantly lower than those in the control group (p < 0.05). Plasma beta-endorphin levels in the control group increased significantly, to 291.8 pg/ml (+/- 6.6 SEM) 5 h after the induction of pancreatitis, from the mean levels of 47.8 pg/ml before the induction of pancreatitis, while the mean beta-endorphin level in the bradykinin receptor antagonist group did not increase after the induction of pancreatitis. Infusion of the bradykinin receptor antagonist improved survival rates, hypotension, myocardial depression, and plasma lactate, suggesting that the bradykinin receptor antagonist inhibited the release of bradykinin and beta-endorphin, which contributed to the clinical improvement.
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PMID:Effects of bradykinin receptor antagonist on the release of beta-endorphin and bradykinin and on hemodynamic changes in a canine model of experimental acute pancreatitis. 892 25

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5'-triphosphate (ATP) at a recombinant P2x2 receptor expressed in defolliculated Xenopus oocytes. 2. Nicotine, 5'-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 microM) potentiated the responses to ATP (3 microM). an effect found due to acidification of the bathing solution by these drugs. 3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 microM) and nerve growth factor (NGF; 50 ng ml-1) potentiated the responses to ATP (3 microM) through a largely or wholly pH-independent effect. 4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate. 5. Since P2x receptors on sensory neurones include P2x2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.
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PMID:Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances. 911 13

A chymostatin-sensitive angiotensin II-generating enzyme was found in human gastroepiploic arteries. The enzyme was purified using heparin affinity and gel filtration columns. The molecular mass of the purified enzyme was 30 kDa, and the optimum pH was between 7.5 and 9.0. Enzyme activity was inhibited by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride and chymostatin, but not by ethylenediaminetetraacetic acid, pepstatin and aprotinin. The enzyme rapidly converted angiotensin I to angiotensin II (K(m), 67 mumol/l; Vmax, 43 pmol/s, kcat, 65/s), but did not hydrolyse angiotensin II, substance P, bradykinin, vasoactive intestinal peptide, luteinizing hormone-releasing hormone, somatostatin and alpha-melanocyte-stimulating hormone. The N-terminal sequence was identical to the sequence for human skin/heart chymase. Thus, the chymostatin-sensitive angiotensin II-generating enzyme in human vascular tissues is identified as chymase.
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PMID:Characterization of chymase from human vascular tissues. 935 25


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