Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous [5-methionine]enkephalin (Metenkephalin) and [5-leucine]enkephalin (Leu-enkephalin) are released from perfused slices of rat globus pallidus by increased K(+) in a Ca(2+)-dependent manner. Tissue perfused for 40 min contained only 26% of the Met-enkephalin and 44% of the Leu-enkephalin found in the freshly dissected tissue. After perfusion, the mean (+/-SEM) ratio (wt/wt) of Met-enkephalin to Leu-enkephalin was 3.4 +/- 0.2 compared with 5.8 +/- 0.2 in the fresh tissue. The degradation of trace amounts of synthetic [(3)H]enkephalins in the perfusing medium during stimulated release seems to reflect the accelerated degradation of enkephalin released from the tissue: 63% of the Met-enkephalin and 23% of the Leu-enkephalin were degraded in a medium containing bacitracin (30 mug/ml). The mean ratio (wt/wt) of the Met-enkephalin to the Leu-enkephalin recovered after release by exposure of slices to 50 mM K(+) was 2.7 +/- 0.3. When perfusates were corrected for degradation, this ratio increased to about 5.5 which is higher than that found in the perfused tissue. The differences in release, tissue loss, and catabolism of the two enkephalins may be reflecting differences in the metabolic systems operating on the pentapeptides, but this interpretation will have to be validated by in vivo release experiments. In any event these observations strongly suggest that both enkephalins can be considered candidate neurotransmitters in the rat globus pallidus.
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PMID:In vitro release of [5-methionine]enkephalin and [5-leucine]-enkephalin from the rat globus pallidus. 27 53

Localization and functional effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), two peptides derived from a common precursor molecule, were investigated in isolated preparations from human penile corpus cavernosum (CC) and circumflex vein (CV). VIP- and PHM-immunoreactivity (IR) was demonstrated in both CC and CV. The concentrations of VIP-IR and PHM-IR in CC tissue were 54.4 +/- 15.3, and 42.0 +/- 7.5 pmol g-1 wet weight respectively with a VIP/PHM ratio of 1.5 +/- 0.4 (mean +/- SEM). The corresponding values for CV tissues were 28.0 +/- 7.7 and 9.6 +/- 2.6 pmol g-1 wet weight with a VIP/PHM ratio of 3.1 +/- 0.4. CC and CV displayed VIP- and PHM-IR confined to nerve fibres in close relation to bundles of smooth muscle cells and blood vessels in both tissues. In vitro, VIP and PHM had no effects in unstimulated tissue preparations. Both peptides concentration-dependently (10(-9)-10(-6) M) relaxed CC and CV preparations precontracted with 3 x 10(-6) M noradrenaline. In CC the maximum relaxant effect of VIP and PHM was 22 +/- 11% and 9 +/- 9% and in CV the corresponding values were 82 +/- 8% and 93 +/- 3% respectively. The present study supports the hypothesis of VIP and PHM as neurotransmitters and/or neuromodulators in the nervous control of penile erection.
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PMID:Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in human penile corpus cavernosum tissue and circumflex veins: localization and in vitro effects. 134 74

We studied whether endothelin-1 (ET-1) would affect its own synthesis. Human umbilical cord vein endothelial cells in methionine-poor culture medium containing [35S] methionine were treated with synthetic ET-1 or ET-3. Immunoprecipitation of 35 S-labeled ET-1 was performed with rabbit ET-1 antiserum. ET-1 caused an 40 +/- 4% (mean +/- SEM) increase of immunoprecipitable 35 S-labeled ET-1 as confirmed by its elution point in reversed phase high power liquid chromatography (HPLC). ET-3 caused a 23 +/- 2% increase in ET-1 concentration. Amplification of cDNA by PCR showed both ET-1 and ETB receptor mRNAs in human cord vein endothelial cells. We conclude that ET-1 increases its own synthesis in endothelial cells. This suggests a positive autocrine feed-back action of ET-1 on its own synthesis, an effect which is probably mediated by non-specific ETB receptors.
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PMID:Endothelin-1 stimulates its own synthesis in human endothelial cells. 141 49

One milliliter of 1, 2, or 5% DL-cysteine (cysteine) or DL-methionine methylsulfonium chloride (MMSC) was instilled into the rat stomach 1, 24, and 48 h after giving ethanol (1 mL of 40% solution) by gavage. One hour following the administration of ethanol, gastric mucosal injury was seen in all the animals (22.6 +/- 1.1 mm2, mean +/- SEM; n = 10). Twenty-four hours after giving the ethanol, all the rats treated with cysteine or MMSC still had the mucosal injury. Treatment with 2% cysteine or MMSC significantly (p less than 0.01) reduced the extent of this injury (10.2 +/- 0.6 and 10.1 +/- 0.5 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10), an action that was similarly achieved by the 5% solutions (10.1 +/- 0.5 and 9.9 +/- 0.3 mm2, respectively, versus 20.7 +/- 1.2 mm2, mean +/- SEM; n = 10). Forty-eight hours following the administration of ethanol, 30% of the animals given 1% cysteine or MMSC still had gastric mucosal injury, which was significantly (p less than 0.001) less extensive than that seen with ethanol alone (3.8 +/- 0.3 and 4.1 +/- 0.3 mm2, respectively, versus 13.1 +/- 0.8 mm2, mean +/- SEM; n = 10). At this time period, however, none of the animals treated with 2 or 5% solutions of cysteine or MMSC still had any injury. Healing of the ethanol-induced injury was confirmed microscopically and was achieved by regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of sulfhydryl-containing agents in the healing of erosive gastritis and chronic gastric ulceration in the rat. 161 73

Phagocytic cells such as alveolar macrophages (AM) or polymorphonuclear neutrophils (PMN) in the bronchoalveolar tract are a potential source of the oxygen-derived free radicals which are presumed to be involved in lung tissue damage. Previous results have shown that the methionine sulphoxide (MET(O)) content of bronchoalveolar lavage fluid (BALF) protein is a reliable parameter to indicate oxidative processes in idiopathic pulmonary fibrosis (IPF). We measured the molar ratio between MET(O) and methionine (MET) in the BALF protein from healthy nonsmokers (control group), healthy smokers and patients with acute or chronic bronchitis (AB or CB). The MET(O)/MET ratio of the nonsmoking group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). Healthy smokers (n = 8) had similar values (0.042 +/- 0.008), even though they had strongly increased AM counts in BALF. Patients with AB (n = 12) showed an increased MET(O)/MET ratio (0.191 +/- 0.031) and had high PMN but normal AM counts in BALF. Patients with CB (n = 13) showed an increase in the MET(O)/MET ratio (0.086 +/- 0.010) and moderately increased PMN and markedly increased AM counts. Taking all results together, the MET(O)/MET ratio correlated positively with the relative PMN number (r = 0.70; p less than 0.0002) and inversely with the relative AM number (r = 0.67; p less than 0.0002). In the group with CB, the MET(O)/MET ratio correlated inversely with forced expiratory volume in one second (FEV1) % pred. (r = -0.77) and FEV1/inspiratory vital capacity (IVC) % pred. (r = -0.89).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased oxidized methionine residues in BAL fluid proteins in acute or chronic bronchitis. 162 21

Intracellular recording techniques were used to study the effects of methionine enkephalin and dynorphin(1-13) on normal circular smooth muscle of human and baboon jejunum. Tetrodotoxin-sensitive inhibitory junction potentials had a mean (+/- SEM) amplitude of 21 +/- 3.3 mV in human jejunum and 24.1 +/- 1.3 mV in baboon jejunum. In both species, exogenously added methionine enkephalin and dynorphin (1-13) decreased inhibitory junction potentials amplitude in a dose-dependent manner with methionine enkephalin being more potent. Both opioid peptides acted on receptors located on axons of intrinsic inhibitory nerves. The effects of both methionine enkephalin and dynorphin(1-13) were blocked by ICI-174,864, a selective delta-receptor antagonist. The selective delta agonist, cyclic [D-penicillamine2, D-penicillamine5]enkephalin, and the selective mu agonist, Try-Pro-NMePhe-D-Pro-NH2, (each 10 mumol/L) decreased inhibitory junction potential amplitude by 79% +/- 6.9% and 61% +/- 4.8%, respectively. The selective kappa agonist, [trans-3,4-dichloro-N-methyl-N-(2-91-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate, (10 mumol/L) had no effect. Although direct postsynaptic opioid receptor blockade of the inhibitory neurotransmitter on the smooth muscle cell has not been ruled out, the authors believe these data suggest that delta and mu receptors were present on inhibitory motor nerves innervating the circular muscle and that methionine enkephalin and dynorphin(1-13) decreased release of inhibitory neurotransmitter(s) by acting on delta receptors.
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PMID:Opioids inhibit neuromuscular transmission in circular muscle of human and baboon jejunum. 167 37

The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day (mean +/- SEM; n = 5) after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by [35S]methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium. The immunoreactive IGFBP-1 isolated from culture medium was found to be identical, by a number of criteria, with IGFBP-1 derived from decidual tissue. These results were consistent with a primary role of progestin exposure, whether in vivo or in vitro, in converting endometrial stromal cells to cells potentially able to exhibit the high rates of IGFBP-1 production typical of the decidualized endometrium of pregnancy.
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PMID:Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells. 170 79

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular responses to activated leukocytes after regression of atherosclerosis. 173 39

Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine and structurally-related compounds. Levels of HNMT activity in the human red blood cell are regulated by inheritance. The inbred mouse is an ideal laboratory animal in which to study the genetics of inherited traits. Therefore, HNMT activity was measured in renal homogenates of A/J mice to establish optimal assay conditions and to determine the properties of mouse kidney HNMT as a first step toward testing the hypothesis that large strain-related variations in HNMT activity might exist among inbred strains of mice. Apparent Km values for histamine and S-adenosyl-L-methionine, the two cosubstrates for the reaction, were 26 and 1.7 microM, respectively. IC50 values for the inhibition of mouse kidney HNMT by amodiaquine and S-adenosyl-L-homocysteine were 1.67 and 11.8 microM, respectively. HNMT activity levels were then measured under optimal assay conditions in renal preparations from male animals of eleven inbred mouse strains chosen because of the availability of recombinant inbred (RI) animals derived from the parental strains. Average values for renal HNMT activity varied among strains by less than two-fold and ranged only from 26.2 +/- 0.51 (mean +/- SEM) units/mg protein in AKR/J mice to 39.1 +/- 2.58 units/mg protein in C57BL/6J animals. Renal HNMT activities in females of the three strains in which both sexes were studied were 11-13% higher than were those in renal tissue from males of the same strain. In summary, the properties of HNMT in the mouse kidney are similar to those of HNMT in other species, but strain variation in levels of enzyme activity among the 11 inbred mouse strains studied was insufficient for these animals to be used in biochemical genetic experiments.
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PMID:Mouse kidney histamine N-methyltransferase: assay conditions, biochemical properties and strain variation. 190 25

Phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases. We assumed that the oxidation of methionine (met) to methionine sulfoxide [met(O)] by oxygen-derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury. To test this hypothesis we determined the molar ratio of met(O)/met in the soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p less than 0.0002). The BAL fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages (AM). In the sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not significantly different from control values. A close relationship was found between the met(O)/met ratios and the relative as well as the absolute neutrophil counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant correlation was found between the met(O)/met ratios and the absolute AM counts (r = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury in IPF can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils.
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PMID:Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis. 199 Sep 39


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