Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine patients with endogenous depression have been treated with infusions of the synthetic methionine enkephaline analogue FK 33-824 for two days. Only on the first day acute effects on depressive symptoms could be observed. It cannot be decided if the observed mood alterations on the first treatment day are placebo effects. Depressive patients showed fewer adverse reactions than healthy volunteers. This might be explained by the previously described greater pain tolerance in depressives.
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PMID:Acute effects of the synthetic analogue of methionine enkephalin FK 33-824 on depressive symptoms. 635 Nov 18

Eukaryotic cell polypeptide chain initiation factor eIF-2 forms ternary complexes with GTP and initiator Met-tRNAf. These complexes can be destabilized in vitro by the addition of salt-washed 40S ribosomal subunits. Our evidence suggests that this destabilization is mediated by GDP generated by premature hydrolysis of the GTP molecule present in the ternary complex. With complexes formed by using a partially purified preparation of eIF-2 from Ehrlich ascites tumor cells, it is possible to reverse the 40S subunit induced inhibition by creating conditions which eliminate free GDP from the system. This reversal probably occurs due to exchange of GTP for the GDP bound to the initiation factor, in a reaction catalyzed by another factor present in the eIF-2 preparation. However, if the eIF-2 has previously been phosphorylated by the reticulocyte heme-controlled repressor, the 40S subunit induced inhibition cannot be reversed by elimination of free GDP. The instability of initiation complexes containing eIF-2, together with the impairment of guanine nucleotide exchange after phosphorylation of eIF-2 [Clemens, M.J., Pain, V.M., Wong, S.-T., & Henshaw, E. C. (1982) Nature (London) 296, 93-95], may be an important aspect of the mechanism of the inhibition of translation by the heme-controlled repressor.
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PMID:Assembly and breakdown of mammalian protein synthesis initiation complexes: regulation by guanine nucleotides and by phosphorylation of initiation factor eIF-2. 655 Nov 77

Formation of the ternary complex Met-tRNAi X eukaryotic initiation factor (eIF) 2 X GTP from eIF-2 X GDP requires exchange of GDP for GTP. However, at physiological Mg2+ concentrations, GDP is released from eIF-2 exceedingly slowly (Clemens, M.J., Pain, V.M., Wong, S.T., and Henshaw, E.C. (1982) Nature (Lond.) 296, 93-95). However, GDP is released rapidly from impure eIF-2 preparations, indicating the presence of a GDP/GTP exchange factor. We have now purified this factor from Ehrlich cells and refer to it as GEF. CM-Sephadex chromatography of ribosomal salt wash separated two peaks of eIF-2 activity. GEF was found in association with eIF-2 in the first peak and co-purified with eIF-2 under low salt conditions. It was separated from eIF-2 in high salt buffers and further purified on hydroxylapatite and phosphocellulose. Gel electrophoresis of our purest preparations showed major bands at 85, 67, 52, 37, 27, and 21 kDa. Purified GEF increased the rate of exchange of [32P] GDP for unlabeled GDP 25-fold but did not function with phosphorylated eIF-2 (alpha subunit). The factor also stimulated markedly the rate of ternary complex formation using eIF-2 X GDP as substrate with GTP and Met-tRNAi but not using phosphorylated eIF-2 X GDP as substrate. eIF-2 is released from the 80 S initiation complex with hydrolysis of GTP. If eIF-2 X GDP is actually the complex released, then GEF is absolutely required for eIF-2 to cycle and it is therefore a new eukaryotic initiation factor. Furthermore, the inability of GEF to utilize eIF-2 (alpha P) X GDP explains how phosphorylation of eIF-2 can inhibit polypeptide chain initiation.
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PMID:A GDP/GTP exchange factor essential for eukaryotic initiation factor 2 cycling in Ehrlich ascites tumor cells and its regulation by eukaryotic initiation factor 2 phosphorylation. 655 52

The influence of a 21 day intermittent footshock regimen upon enkephalin levels in brain and adrenals was examined in the rat. Changes in pain sensitivity as well as analgesic and hyperthermic responsiveness to morphine (7.5 mg/kg) were also monitored. Following the stress regimen, Met and Leu enkephalin levels were decreased by 40 to 50% in brain, but were unchanged in adrenals. Post-stress pain thresholds were markedly decreased in stressed animals while the analgesic properties of morphine were enhanced. Core body temperature of stressed animals was significantly raised, but the hyperthermic response to morphine was unchanged.
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PMID:Prolonged intermittent footshock stress decreases Met and Leu enkephalin levels in brain with concomitant decreases in pain threshold. 686 48

Metkephamid is an analog of methionine enkephalin. The efficacy, safety, and time course of analgesia with 70 or 140 mg metkephamid were compared with those of 100 mg meperidine and placebo in 59 hospitalized women with severe postpartum episiotomy pain. There were two separate trials with single intramuscular doses and identical designs, including parallel groups, randomized blocks, and double-blind conditions. Using subjective reports as indexes of response, patients rated pain intensity, pain relief, and side effects at periodic interviews for 6 hr. Almost all measures of summed and peak analgesia exhibited important differences among the three treatments in both trials. Metkephamid at the 140-mg dose was the most effective and meperidine, 100 mg, was next, whereas metkephamid, 70 mg, and placebo were least effective. Only metkephamid, 140 mg, and meperidine were measurably superior to placebo. Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine. Metkephamid, 70 mg, could not be distinguished from placebo throughout its entire time course. Although dizziness was experienced with meperidine, the two metkephamid doses induced other side effects, including sensation of heavy limbs, dry mouth, eye redness, and nasal stuffiness. None were distressing. Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently.
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PMID:Metkephamid and meperidine analgesia after episiotomy. 687 19

[Met]Enkephalin-Arg6-Phe7 is an opiate-like peptide normally found in the the adrenal gland and brain that has analgesic (antinociceptive) activity when administered directly into the cerebral ventricles of mice. On a molar basis, [Met]-enkephalin-Arg6-Phe7, with a median effective dose (ED50) of 38.5 nmol/mouse, is 8 times more potent than [Met]enkephalin. As with [Met]enkephalin, analgesic activity is blocked by naloxone and intravenous administration does not produce characteristic opiate effects in tests for analgesic, antidiuretic, or antidiarrheal activity. These findings suggest that [Met]enkephalin-Arg6-Phe7 may be at least as important as the enkephalins in the postulated enkephalin system mediating pain and analgesia.
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PMID:Analgesic activity of the naturally occurring heptapeptide [Met]enkephalin-Arg6-Phe7. 693 69

The small endogenous peptides, Met- and Leu-enkephalin, bind to the same specific receptors as opiate analgesics. They, and the larger endorphin peptides, have been widely found in mammals, where they seem to have a significant role in neuronal pathways mediating pain and emotional behaviour. Only recently has enkephalin-like activity been identified in an invertebrate, the earthworm, although there is some preliminary evidence for opiate receptors in a marine mollusc. Here I report the detection, by an immunocytochemical technique, of an enkephalin-like moiety which is localised in one of the 400 cells of each posterior midbody ganglion of the leech. The presence of enkephalin-like activity in an identifiable easily accessible neurone of a well characterised nervous system such as that of the leech could greatly facilitate elucidation of its mechanism of action.
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PMID:Identification of specific leech neurones immunoreactive to enkephalin. 698 25

The authors measured endorphin levels in the cerebrospinal fluid (CSF) of 12 patients with chronic pain due to lumbar disc syndrome and eight patients with acute postoperative pain. These were compared with CSF endorphin levels in 20 control patients with no history of pain. Endorphins were extracted by adsorption to a synthetic resin (Amberlite XAD-2), eluted with methanol, and assayed using the electrically stimulated mouse vas deferens. Results were expressed as methionine-enkephalin (Met-E) equivalents, which was the standard in the bioassay. The CSF endorphin level was 0.42 +/- 0.07 pmol/ml (mean +/- SE) in the postoperative group, 1.44 +/- 0.2 pmol/ml in the chronic pain group, and 4.36 +/- 0.89 pmol/ml in the control group. CSF endorphin levels in the two pain groups differed significantly from both the control group and each other. These results suggest a correlation between pain levels and endorphin concentration in the CSF; however, in the acute postoperative pain group the influence of other factors such as anesthesia or surgical stress cannot be evaluated.
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PMID:Endorphin levels in cerebrospinal fluid of patients with postoperative and chronic pain. 709 14

Endorphin levels in human cerebrospinal fluid (CSF) have been determined by using the electrically stimulated mouse vas deferens bioassay. Endorphins were extracted by adsorption to a synthetic resin of Amberlite XAD-2 eluted with methanol, and dried under a nitrogen atmosphere. Three different groups of patients have been studied: a) control subjects without a history of pain (n = 25), b) patients with acute postoperative pain after high abdominal and thoracic surgery (n = 8) and c) patients with chronic pain due to discal hernia (n = 14). The endorphin levels (expressed as equivalents of Met-E) obtained from the control group were 4.36 +/- 0.7 pmol/ml. In the postoperative group an endorphin decrease of 0.42 +/- 0.07 pmol/ml, was found while in the chronic pain group the levels obtained were 1.39 +/- 0.2 pml/ml. Thus a significantly low level of CSF endorphins was observed in both the postoperative and the chronic pain group as compared with the controls (p less than 0.01). These results suggest a correlation between pain levels and endorphin concentration in CSF. However in the acute postoperative pain group other factors such as depletion of endorphins by drugs used for anesthesia or due to surgical stress cannot be excluded.
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PMID:[Measurement of endorphins in human cerebrospinal fluid. Comparative study of various groups of patients]. 715 54

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.
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PMID:Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase. 720 49


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