Comparative study on analgesic effect of Met5-enkephalin and related lipotropin fragments

Gráf, László; Székely, József I.; Rónai, András Z.; Dunai-Kovács, Zsuzsa; Bajusz, S.

doi:10.1038/263240a0

Cited by 145 publications

(16 citation statements)

References 12 publications

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“…The distinct differences in the response to divalent cations and potencies of the various peptides and alkaloid in displacing the 3H-labeled ligands suggests a difference in the binding sites between f3-endorphin and enkephalin. This dissimilarity in the nature of these peptides' binding also suggests that rapid hydrolysis of enkephalin by brain homogenates (25) might not be the sole explanation for the lack of in vivo analgesic effect displayed by the pentapeptide (11,26). Although [D-Ala2 [Metlenkephalin had potent in vivo analgesic effect (27), the alteration in the secondary structure of the peptide (28) by the D amino acid could not be ignored.…”

Section: Methodsmentioning

confidence: 99%

Properties and localization of beta-endorphin receptor in rat brain.

Law¹,

Loh²,

1979

Proc. Natl. Acad. Sci. U.S.A.

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Thus, by using such a washing procedure with the rapid filtration method, we were able to demonstrate a proteindependent and temperature-dependent high-affinity association of the 13h-[3H]endorphin with the brain membrane (7). Moreover, this high-affinity binding can be demonstrated to be stereospecific (7). The stereoactive isomer levorphanol or (-)naloxone was at least 1000-fold more potent in displacing 3h-[3H]endorphin binding than was the inactive isomer dextrorphan or (+)naloxone, respectively. When the binding of this radioactive ligand was determined at various concentrations and the binding data were analyzed by the method of Scatchard (10), a two-component or single site with negative cooperativity typical of the opiate binding was observed (Fig. 1). The Kd values (with 95% confidence limits) determined from linear regression analysis of the two binding Abbreviation: LPH, lipotropin. 5455The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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Section: Methodsmentioning

confidence: 99%

Properties and localization of beta-endorphin receptor in rat brain.

Law¹,

Loh²,

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…SMYTH obtained in rats (Graf, Szekely, Ronai, Dunai-Kovacs & Bajusz, 1976;Loh, Tseng, Wei & Li, 1976;Van Ree, de Wied, Bradbury, Hulme, Smyth & Snell, 1977;Bradbury, Smyth, Snell, Deakin & Wendlandt, 1977).…”

Section: Introductionmentioning

confidence: 99%

C‐fragment of Lipotropin—an Endogenous Potent Analgesic Peptide

Feldberg

Smyth

1977

British J Pharmacology

121

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I A series of peptides derived from porcine lipotropin was examined for analgesic and other morphine-like properties on infusion into the cannulated third ventricle of cats. 2 Lipotropin (LPH 1-91) itself produced no analgesia or other morphine-like effects when infused in a dose of 150 pg.3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 jg; on a molar basis the potency was between 90 and 180 times that of morphine. The following morphine-like effects were also produced: shivering leading to fever, vasodilatation of the pinnae, mydriasis, opening of the palpebral fissures, tachypnoea with bouts of panting, vocalization, hyperexcitability, restlessness and catalepsy. All the effects, including analgesia, were abolished by an intraperitoneal injection of naloxone (1 mg/kg). 4 Hyperglycaemia, another central effect produced by morphine, was obtained with C-fragment infused in a dose of 60 pg. 5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 gg/kg.Administered by this route, C-fragment was again more potent than morphine. 6 C'-fragment (LPH 61-87), LPH 61-78 and LPH 61-69, either had no analgesic effect or produced weak short-lasting analgesia when infused in doses up to 100 jg. 7 Methionine enkephalin (LPH 61-65) either produced very weak short-lasting analgesia or had no analgesic effect when infused in doses of between 30 and 400 jig. 8 N-methyl methionine enkephalin amide in which both termini of methionine enkephalin were protected against degradation by exopeptidases produced long-lasting analgesia when infused in doses of 150 to 180 jig; its analgesic potency was approximately 100 times less than that of C-fragment.Blocking only one terminus of methionine enkephalin did not appear to endow the peptide with analgesic properties. The N-methyl pentapeptide amide produced other morphine-like effects of which the most striking was catalepsy. All the effects were abolished by intraperitoneal naloxone (1 mg/kg).

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“…Peptides with opiate-like properties have been isolated from brain and pituitary, and their sequences and structures have been confirmed by complete synthesis (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). The naturally occurring enkephalins and endorphins share common NH2-terminal sequences with COOH-terminal fragments of p-lipotropin (f3-LPH).…”

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confidence: 99%

Regional dissociation of beta-endorphin and enkephalin contents in rat brain and pituitary.

Rossier¹,

Vargo²,

Minick³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

376

105

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beta-Endorphin and enkephalin in extracts of whole brain, various brain regions, adenohypophysis, and combined pars intermedia and neurohypophysis of the rat were measured by radioimmunoassay. In brain extracts, the immunoreactive substances were further separated according to molecular size by gel filtration. beta-Endorphin was found in the diencephalon but not in the hippocampus, cerebral cortex, cerebellum, and striatum. Enkephalin was found predominantly in the striatum and diencephalon. Attention is called to possible artifactual interference by myelin basic protein in the immunoassays for beta-endorphin in some regions of the brain. In the pituitary, enkephalin was mainly restricted to the pars intermedia-neurohypophysis. Neither adrenalectomy nor hypophysectomy significantly altered levels of beta-endorphin in brain extracts. Adrenalectomy increased the levels of beta-endorphin in adenohypophysis and pars intermedia-neurohypophysis; after adrenalectomy, enkephalin was also increased in the adenohypophysis but less so in the pars intermedia-neurohypophysis. These results show that brain endorphin levels are independent of pituitary endorphin levels; they suggest that beta-endorphin-containing neurons and those containing enkephalin constitute two separate groups of brain cells.

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Comparative study on analgesic effect of Met5-enkephalin and related lipotropin fragments

Cited by 145 publications

References 12 publications

Properties and localization of beta-endorphin receptor in rat brain.

Properties and localization of beta-endorphin receptor in rat brain.

C‐fragment of Lipotropin—an Endogenous Potent Analgesic Peptide

Regional dissociation of beta-endorphin and enkephalin contents in rat brain and pituitary.

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