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Leon F Tseng - One of the best experts on this subject based on the ideXlab platform.
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intrathecal cholecystokinin octapeptide attenuates the antinociception and release of immunoreactive met enkephalin induced by intraventricular β endorphin in the rat
Neuropeptides, 1992Co-Authors: K A Collins, Leon F TsengAbstract:Abstract The effects of cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) on antinociception and the release of immunoreactive Met-Enkephalin in the spinal perfusate induced by intraventricular (i.vt.) injection of β-endorphin were studied in anesthetized rats. β-Endorphin (5 μg) given i.vt. inhibited the tail-flick response. The inhibition of the tail-flick response induced by β-endorphin was blocked dose-dependently by CCK8s (0.1–7 μg) given i.t. The antagonistic effect of CCK8s on β-endorphin-induced inhibition was blocked dose dependently by co-intrathecal injection of proglumide (3 and 10 μg), a CCK8s receptor antagonist. β-Endorphin (5 μg) given i.vt. elicited a release of immunoreactive Met-Enkephalin in the spinal perfusate. Repeated injections of the same dose of β-endorphin released about the same amount of the immunoreactive Met-Enkephalin in the spinal perfusate. CCK8s at concentrations from 1 × 10 −9 to 1 × 10 −6 M added into the spinal perfusate decreased the release of Met-Enkephalin induced by β-endorphin given i.vt. in a dose-dependent manner. The results suggest that CCK8s may attenuate β-endorphin-induced inhibition of the tail-flick response by inhibiting the release of Met-Enkephalin from the spinal cord.
N Stambuk - One of the best experts on this subject based on the ideXlab platform.
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Cytoprotective effects of Met-Enkephalin and alpha-MSH on ethanol induced gastric lesions in rats.
Journal of physiology Paris, 2020Co-Authors: P Konjevoda, N Stambuk, G Aralica, B PokrićAbstract:We used the rat model of ethanol induced gastric lesions to measure cytoprotective effects of neuropeptides Met-Enkephalin and alpha-melanocyte stimulating hormone (alpha-MSH). The lesions were induced with i.g. application of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol. Sacrifice was made 1 h after ethanol application and hemorrhagic gastric area was assessed in mm(2). alpha-MSH and Met-Enkephalin exhibited significant and additive cytoprotective effects. The protective effects of alpha-MSH were significantly stronger than of Met-Enkephalin. Almost total absence of lesions was obtained with Met-Enkephalin and alpha-MSH mixture 10:1 (10 mg/kg Met-Enkephalin and 1 mg/kg alpha-MSH). The addition of indomethacin (5 mg/kg s.c.) almost completely abolished the effect of met-enkaphalin, while alpha-MSH mediated cytoprotection was weakened but still present. Interestingly, indomethacin also blocked almost completely the cytoprotective effects of Met-Enkephalin and alpha-MSH mixture. The latter result may have a practical consequence for the clinical trials in which Met-Enkephalin and alpha-MSH could be used in combination with non-steroidal anti-inflammatory drugs.
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Cytoprotective effects of Met-Enkephalin and α-MSH on ethanol induced gastric lesions in rats
Journal of Physiology-paris, 2020Co-Authors: P Konjevoda, N Stambuk, G Aralica, B PokrićAbstract:We used the rat model of ethanol induced gastric lesions to measure cytoprotective effects of neuropeptides Met-Enkephalin and α-melanocyte stimulating hormone (α-MSH). The lesions were induced with i.g. application of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol. Sacrifice was made 1 h after ethanol application and hemorrhagic gastric area was assessed in mm2. α-MSH and Met-Enkephalin exhibited significant and additive cytoprotective effects. The protective effects of α-MSH were significantly stronger than of Met-Enkephalin. Almost total absence of lesions was obtained with Met-Enkephalin and α-MSH mixture 10:1 (10 mg/kg Met-Enkephalin and 1 mg/kg α-MSH). The addition of indomethacin (5 mg/kg s.c.) almost completely abolished the effect of met-enkaphalin, while α-MSH mediated cytoprotectipon was weakened but still present. Interestingly, indomethacin also blocked almost completely the cytoprotective effects of Met-Enkephalin and α-MSH mixture. The latter result may have a practical consequence for the clinical trials in which Met-Enkephalin and α-MSH could be used in combination with non-steroidal anti-inflammatory drugs.
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Protective effects of Met-Enkephalin on alcohol induced gastric lesions
Croatica Chemica Acta, 2020Co-Authors: P Konjevoda, N Stambuk, Dražen Vikić-topić, Alenka Boban-blagaić, Smiljka Vikić-topić, Vladimir Mrljak, Pero Ramadan, Zdenko BiđinAbstract:The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-Enkephalin (Peptid-M, LUPEXŇ) and a-melanocyte stimulating hormone (a-MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The bect therapeutic efficacy was obtained with Met-Enkephalin and a-MSH mixture 3-5 : 1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide fractions, Thymus Peptide Câ and JAN 50â. Thymus Peptide Câ exhibited significant synergistic effect with Met-Enkephalin while JAN 50â did not. In addition to the cytoprotection of rat gastric mucosa Met-Enkephalin also induced statistically significant and dose dependent Straub tail response versus control (in mice). Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic findings of Met-Enkephalin and haloperidol confirmed molecular interactions of both substances.
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Met-Enkephalin modifies respiratory function in guinea-pigs
Journal of Cystic Fibrosis, 2020Co-Authors: Dorian Tješić-drinković, N Stambuk, P KonjevodaAbstract:Aim: Met-Enkephalin is an endogenous opioid pentapeptide with cytokine properties that has been investigated in many in vitro and in vivo models of inflammation. This study was conducted in order to examine the possible effect of met- enkephalin on changes in pulmonary function provoked by histamine. Methods: Experimental animals were Hartley guinea-pigs (6 animals per group, male-female 1:1, weight 500-700g). Classic Konzett and Rossler’ s method of whole body plethysmography modified by Gjuris was applied to monitor changes in the respiratory rate, type of respirations or amplitude of respirations. Bronchoconstriction was induced in anesthetized animals by i.v. histamine (10 μ g/kg) and the protective effect of Met-Enkephalin was defined as the percentage of histamine blockade (the reduction of histamine-induced bronchoconstriction ; each animal its own control). Three doses of Met-Enkephalin were applied: 0.1 mg/kg, 1 mg/kg, and 10 mg/kg. Data were compared by t-test. Results: Met-Enkephalin doses of 1 mg/kg and 10 mg/kg caused significant reduction of the histamine induced bronchoconstriction (p
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Met-Enkephalin therapy for autoimmune diseases: Selective immunomodulation and extention of steroid therapy
1999Co-Authors: N Stambuk, Vesna V. Brinar, Branka Marušić-della Marina, Vjera Štambuk, Ksenija Karaman, Zdravko Brzović, Niko Zurak, Tanja Marotti, Višnja Šverko, Sabina RabatićAbstract:Met-Enkephalin is a pentapeptide present in different tissues. This neuropeptide exerts various modulatory signals on different cell types, which led to its application in clinical medicine (Plotnikoff et al., Clin Immunol Immunopathol, 82:93, 1997 ; Stambuk et al., Uveitis Today, Elsevier, Amserdam, pp 319-322, 1998). The authors review Met-Enkephalin therapy in 38 patients with autoimmune diseases (uveitis, Behcet's disease, allergic conjunctivitis/rhinitis, optic neuritis, multiple sclerosis, SLE/overlap syndrome, rheumatoid arthritis, Evans syndrome/hemolytic anemia). No toxicity or side-effects were observed during the Met-Enkephalin therapy ranging from 6 months to >3 years. Met-Enkephalin (peptid-M, LUPEX) was administered s.c. dissolved in 2 ml of physiological saline, 0.2 - 0.3 mg/kg 5 times weekly for 4 weeks. Afterwards, the weekly dose was gradually reduced every 4 weeks till 5 mg weekly. Clinical parameters including EDSS, evoked potentials, visual field, MRI and ultrasonographic findings were observed and evaluated to obtain better insight into the efficacy of Met-Enkephalin therapy. In addition to the beneficial clinical effects and significant reduction in the number and severity of relapses the peptide modulated serum IFN, IFN-gamma, phagocyte, NK and lymphocyte functions. During Met-Enkephalin therapy relapses were rare, mild, and in most cases did not require additional corticosteroid therapy, i.e. only the rise of Met-Enkephalin dose was sufficient. However, the synergistic action of Met-Enkephalin and corticosteroids is discussed considering the fact that it is a part of ACTH precursor molecule (Blalock, Immunol Today 15:504, 1994). It is emphasised that in severe autoimmune diseases parallel administration of Met-Enkephalin and corticosteroids enables significant reduction of the steroid dose (to e.g. 2-4 mg dexamethasone daily during relapse). Treatment protocols for combined immunotherapy of Met-Enkephalin and corticosteroids or i.v. IgG (7S, 5S+7S) have also been defined (Stambuk et al., Int J Thymology 5:448, 1997). Finally, we re-evaluate classic opioid hypothesis of Met-Enkephalin action considering Met-Enkephalin interactions with its probable calpastatin receptor site, that was recently defined by means of the Molecular Recognition Theory (Stambuk et al., Croat Chem Acta 71:591, 1998). This sequence shares homology to the Rapamycin and FK506 receptor site (FKB3_HUMAN, aa 108-111), which may account for the immuno-suppressive effects of Met-Enkephalin in vitro and in vivo independently of the opioid system and without mutagenetic effects.
K A Collins - One of the best experts on this subject based on the ideXlab platform.
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intrathecal cholecystokinin octapeptide attenuates the antinociception and release of immunoreactive met enkephalin induced by intraventricular β endorphin in the rat
Neuropeptides, 1992Co-Authors: K A Collins, Leon F TsengAbstract:Abstract The effects of cholecystokinin octapeptide (CCK8s) given intrathecally (i.t.) on antinociception and the release of immunoreactive Met-Enkephalin in the spinal perfusate induced by intraventricular (i.vt.) injection of β-endorphin were studied in anesthetized rats. β-Endorphin (5 μg) given i.vt. inhibited the tail-flick response. The inhibition of the tail-flick response induced by β-endorphin was blocked dose-dependently by CCK8s (0.1–7 μg) given i.t. The antagonistic effect of CCK8s on β-endorphin-induced inhibition was blocked dose dependently by co-intrathecal injection of proglumide (3 and 10 μg), a CCK8s receptor antagonist. β-Endorphin (5 μg) given i.vt. elicited a release of immunoreactive Met-Enkephalin in the spinal perfusate. Repeated injections of the same dose of β-endorphin released about the same amount of the immunoreactive Met-Enkephalin in the spinal perfusate. CCK8s at concentrations from 1 × 10 −9 to 1 × 10 −6 M added into the spinal perfusate decreased the release of Met-Enkephalin induced by β-endorphin given i.vt. in a dose-dependent manner. The results suggest that CCK8s may attenuate β-endorphin-induced inhibition of the tail-flick response by inhibiting the release of Met-Enkephalin from the spinal cord.
P Konjevoda - One of the best experts on this subject based on the ideXlab platform.
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Cytoprotective effects of Met-Enkephalin and alpha-MSH on ethanol induced gastric lesions in rats.
Journal of physiology Paris, 2020Co-Authors: P Konjevoda, N Stambuk, G Aralica, B PokrićAbstract:We used the rat model of ethanol induced gastric lesions to measure cytoprotective effects of neuropeptides Met-Enkephalin and alpha-melanocyte stimulating hormone (alpha-MSH). The lesions were induced with i.g. application of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol. Sacrifice was made 1 h after ethanol application and hemorrhagic gastric area was assessed in mm(2). alpha-MSH and Met-Enkephalin exhibited significant and additive cytoprotective effects. The protective effects of alpha-MSH were significantly stronger than of Met-Enkephalin. Almost total absence of lesions was obtained with Met-Enkephalin and alpha-MSH mixture 10:1 (10 mg/kg Met-Enkephalin and 1 mg/kg alpha-MSH). The addition of indomethacin (5 mg/kg s.c.) almost completely abolished the effect of met-enkaphalin, while alpha-MSH mediated cytoprotection was weakened but still present. Interestingly, indomethacin also blocked almost completely the cytoprotective effects of Met-Enkephalin and alpha-MSH mixture. The latter result may have a practical consequence for the clinical trials in which Met-Enkephalin and alpha-MSH could be used in combination with non-steroidal anti-inflammatory drugs.
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Cytoprotective effects of Met-Enkephalin and α-MSH on ethanol induced gastric lesions in rats
Journal of Physiology-paris, 2020Co-Authors: P Konjevoda, N Stambuk, G Aralica, B PokrićAbstract:We used the rat model of ethanol induced gastric lesions to measure cytoprotective effects of neuropeptides Met-Enkephalin and α-melanocyte stimulating hormone (α-MSH). The lesions were induced with i.g. application of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol. Sacrifice was made 1 h after ethanol application and hemorrhagic gastric area was assessed in mm2. α-MSH and Met-Enkephalin exhibited significant and additive cytoprotective effects. The protective effects of α-MSH were significantly stronger than of Met-Enkephalin. Almost total absence of lesions was obtained with Met-Enkephalin and α-MSH mixture 10:1 (10 mg/kg Met-Enkephalin and 1 mg/kg α-MSH). The addition of indomethacin (5 mg/kg s.c.) almost completely abolished the effect of met-enkaphalin, while α-MSH mediated cytoprotectipon was weakened but still present. Interestingly, indomethacin also blocked almost completely the cytoprotective effects of Met-Enkephalin and α-MSH mixture. The latter result may have a practical consequence for the clinical trials in which Met-Enkephalin and α-MSH could be used in combination with non-steroidal anti-inflammatory drugs.
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Protective effects of Met-Enkephalin on alcohol induced gastric lesions
Croatica Chemica Acta, 2020Co-Authors: P Konjevoda, N Stambuk, Dražen Vikić-topić, Alenka Boban-blagaić, Smiljka Vikić-topić, Vladimir Mrljak, Pero Ramadan, Zdenko BiđinAbstract:The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-Enkephalin (Peptid-M, LUPEXŇ) and a-melanocyte stimulating hormone (a-MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The bect therapeutic efficacy was obtained with Met-Enkephalin and a-MSH mixture 3-5 : 1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide fractions, Thymus Peptide Câ and JAN 50â. Thymus Peptide Câ exhibited significant synergistic effect with Met-Enkephalin while JAN 50â did not. In addition to the cytoprotection of rat gastric mucosa Met-Enkephalin also induced statistically significant and dose dependent Straub tail response versus control (in mice). Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic findings of Met-Enkephalin and haloperidol confirmed molecular interactions of both substances.
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Met-Enkephalin modifies respiratory function in guinea-pigs
Journal of Cystic Fibrosis, 2020Co-Authors: Dorian Tješić-drinković, N Stambuk, P KonjevodaAbstract:Aim: Met-Enkephalin is an endogenous opioid pentapeptide with cytokine properties that has been investigated in many in vitro and in vivo models of inflammation. This study was conducted in order to examine the possible effect of met- enkephalin on changes in pulmonary function provoked by histamine. Methods: Experimental animals were Hartley guinea-pigs (6 animals per group, male-female 1:1, weight 500-700g). Classic Konzett and Rossler’ s method of whole body plethysmography modified by Gjuris was applied to monitor changes in the respiratory rate, type of respirations or amplitude of respirations. Bronchoconstriction was induced in anesthetized animals by i.v. histamine (10 μ g/kg) and the protective effect of Met-Enkephalin was defined as the percentage of histamine blockade (the reduction of histamine-induced bronchoconstriction ; each animal its own control). Three doses of Met-Enkephalin were applied: 0.1 mg/kg, 1 mg/kg, and 10 mg/kg. Data were compared by t-test. Results: Met-Enkephalin doses of 1 mg/kg and 10 mg/kg caused significant reduction of the histamine induced bronchoconstriction (p
Kohichi Kojima - One of the best experts on this subject based on the ideXlab platform.
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adrenal opioid proteins of 8600 an in proenkephalin processing enkephalin opioid peptide adrenal medulla tryptic mapping mici
2016Co-Authors: Barry N Jones, Sidney Udenfriend, Alvin S Stern, E John, Daniel L Kilpa, Kohichi Kojima, Randolph V LewisAbstract:Met)Enkephalin-containing proteins of 8600 and 12,600 daltons have been isolated from acid extracts of bovine adrenal medulla and purified to homogeneity, and their sequences have been determined by a combination of automated Edman degradation, tryptic mapping, and enzymatic time-course hy- drolysis. The 8600-dalton protein contains one copy of the (Met)enkephalin sequence at the COOH terminus and the 12,600- dalton protein contains three copies of!(Met)enkephalin, of which two are internal and the third,is at the COOH terminus. They possess identical NH2-terminal amino acid sequences, suggesting that the 8600-dalton protein is derived from the 12,600-dalton protein by intracellular proteolytic processing. This is supported by results from tryptic maps of both proteins. Furthermore, chem- ical analysis of the tryptic peptides obtained from the 12,600-dal- ton protein indicates that it also contains the amino acid sequence that corresponds to a previously characterized enkephalin-con- taining polypeptide of 3800 daltons (peptide F) (Jones et al. (1980) Arch. Biochem. Biophys. 204, 392-395). All three polypeptides appear to be intermediates in posttranslational processing of a still larger polyenkephalin precursor molecule, proenkephalin, and part of a biosynthetic pathway leading to smaller enkephalin-con- taining polypeptides and free enkephalins.
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enkephalin biosynthetic pathway polypeptide that terminates at its c sequence metlenkephalin arg gly opioid peptide adrenal medulla microsequence determination
2016Co-Authors: Barry N Jones, Sidney Udenfriend, E John, Daniel L Kilpa, Kohichi KojimaAbstract:An enkephalin-containing polypeptide of 5300 daltons has been isolated from extracts of bovine adrenal medulla and purified to homogeneity, and its sequence has been deter- mined by a combination of automated Edman degradation and enzymatic time-course hydrolysis. The polypeptide contains a sin- gle (Met)enkephalin sequence followed by Arg-Gly-Leu-COOH, which forms the COOH terminus of the molecule. The enkephalin sequence is preceded by a Lys-Arg linkage, typical of prohormone cleavage sites. Posttranslational processing of the polypeptide at this site would lead to release of the octapeptide (Met)enkephalin- Arg6-Gly7 -Leus