The C-terminal dipeptide of β-endorphin: A neuropeptide with inhibitory activity

Smyth, Derek G.; Parish, David C.; Normanton, J.R.; Wolstencroft, J. H.

doi:10.1016/0024-3205(83)90568-4

Cited by 12 publications

(6 citation statements)

References 1 publication

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“…Specifically, reward sites showing both beta-endorphin nerve terminals and responsiveness to GQ include NAC, ventral tegmental area, and the central nucleus of the amygdala (GQ data not shown). The endogenous role for GQ is further supported by the finding that the dipeptide is made from post-translational cleavage of β-endorphin(1-31) and the isolation of GQ and beta-endorphin from brain tissue [14,21]. These findings are consistent with the demonstration of PC2 enzyme cleavage of β-endorphin(1-31) into GQ and a number of 26 and 27 amino acid shortened β-endorphin peptides [7].…”

Section: Endogenous Gqsupporting

confidence: 71%

Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague–Dawley rats

Resch¹,

Simpson²

2008

Peptides

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Peptide inhibitors of ethanol consumption have shown promise. The purpose of this study was to test the cyclized form of the opioid-derived dipeptide, glycyl-L-glutamine to reduce ethanol consumption after either peripheral injections or site-specific injections into the nucleus accumbens (NAC) of high drinking and low drinking rats. Following I.P. cyclo-glycyl-glutamine (c-GQ), the data show a mean decrease in ethanol intake of 34.4% in P rats, and 39.4% in Sprague-Dawley rats at doses between 5 and 25mg/kg. The data show that peripherally administered c-GQ is effective in reducing ethanol consumption in both high (P) and low (SD) drinking strains of rats and suggests a therapeutic potential.

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Section: Endogenous Gqsupporting

confidence: 71%

Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague–Dawley rats

Resch¹,

Simpson²

2008

Peptides

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“…Additional studies will be required to determine the lowest effective doses. Further, the 1 fmol to 1 pmol doses imply that responsiveness to GQ may be in a physiological range, and is consistent with levels from tissue extracts which contained 2.23 pmol GQ per gram of tissue Smyth et al, 1983). The sensitivity of the CeM and VTA suggest the possibility that these sites may be a normal endogenous target for a GQ modulator attenuating drinking.…”

Section: Characteristics Of Gq Actionsupporting

confidence: 67%

Glycyl-glutamine reduces ethanol intake at three reward sites in P rats

Resch¹,

Simpson²

2008

Alcohol

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Abstractβ-endorphin, implicated in modulation of ethyl alcohol reward, has neuron terminals in several reward sites. Alcohol consumption was reduced after ventricular or site specific injections into the nucleus accumbens of an opioid-derived dipeptide, glycyl-glutamine. The current study examined the effects of this dipeptide after site specific injections into additional reward sites. Alcohol preferring (P) rats, stereotaxically implanted with bilateral guide cannulae into the nucleus accumbens, ventral tegmental area, and the central nucleus of the amygdala were given 30% alcohol and water in a 24 h voluntary 2-bottle choice paradigm. Upon achieving stable baseline intakes, glycyl-glutamine (GQ) doses were injected bilaterally, and the alcohol and water intakes and body weight recorded for the response and recovery. The data show reduced alcohol intake by 32 to 49.5% after 100 pmol glycyl-glutamine into reward sites (nucleus accumbens, ventral tegmental area, and central nucleus of the amygdala), but not after injections into control sites dorsal to reward sites. The order of sensitivity to the 1 fmol dose was amygdala ≥ ventral tegmental area > accumbens. GQ was effective in reducing ethanol intake at reported β-endorphin terminal regions in each of the three reward sites tested. The effective doses were similar to reported endogenous GQ levels, consistent with the notion that it may function as part of an endogenous counter regulatory mechanism and represent a "stop drinking" signal in the high drinking, alcohol preferring P rats at these three reward sites.

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“…Two cleavage products of β-endorphin 1-31 – β-endorphin1-27 and Gly-Gln (β-endorphin 30-31) – are implicated in reduction of ethanol intake [1; 2; 3; 4; 5; 6]. β-endorphin1-27 and Gly-Gln act in different ways.…”

mentioning

confidence: 99%

“…All these findings corroborate the fact that Gly-Gln has an interesting and potentially useful pharmacological activity. Gly-Gln has previously been quantitated in sheep and pig pituitary gland using radioimmunoassay (RIA) [1; 2]. Given the widespread availability LC-MS/MS technology, and its relative ease of use and lack of requirement for radiolabeled analytes, we felt it would be beneficial to develop an LC-MS/MS assay for detection and quantification of Gly-Gln in the brain.…”

mentioning

confidence: 99%

A liquid chromatography–tandem mass spectrometry assay for detection and quantitation of the dipeptide Gly-Gln in rat brain

Bobba

Resch

Gutheil

2012

Analytical Biochemistry

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The enzymatic cleavage products of β-endorphin (β-endorphin1-27 and Gly-Gln) reduce voluntary alcohol consumption in alcohol preferring P rats. Gly-Gln also inhibits the reward benefiting effects of morphine and nicotine. It would be useful for the investigation of this effect to have an analytical method suitable for Gly-Gln detection and quantitation. Given the now widespread availability of LC-MS/MS instruments, the development of an LC-MS/MS-based approach seemed a viable option. An LC-MS/MS method for Gly-Gln quantitation was developed based on derivatization with Marfey’s reagent. The Marfey’s adduct of Gly-Gln (Mar-Gly-Gln) was chromatographically resolved and readily detected and quantitated by LC-MS/MS. Precursor/product positive ions of 456.2/366.2, 456.2/237.2, 456.2/147.0 were used for detection and quantitation. This method shows good linearity from 1 to 500 pmole of Mar-Gly-Gln (R2 >0.99). The assay also demonstrated good accuracy and precision, with an average percent standard deviation for Gly-Gln over the range of the assay of <5%. A combination of MRM fragment ratio normalization and chromatographic peak shifting were used to ensure that the LC-MS/MS peak for Mar-Gly-Gln was free from possible isobar interferences. This assay was then demonstrated for the determination of in vivo Gly-Gln levels in P and Sprague-Dawley rat cortex and nucleus accumbens samples.

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The C-terminal dipeptide of β-endorphin: A neuropeptide with inhibitory activity

Cited by 12 publications

References 1 publication

Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague–Dawley rats

Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague–Dawley rats

Glycyl-glutamine reduces ethanol intake at three reward sites in P rats

A liquid chromatography–tandem mass spectrometry assay for detection and quantitation of the dipeptide Gly-Gln in rat brain

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