Beta-Endorphin-Induced Cardiorespiratory Depression is Inhibited by Glycyl-L-Glutamine, a Dipeptide Derived from Beta-Endorphin Processing. Appendix 1

Ünal, Can; Owen-Kummer, Medge D; Millington, William R.

doi:10.21236/ada283495

Cited by 16 publications

(22 citation statements)

References 32 publications

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“…These data extend earlier evidence that Gly-Gln attenuates the hypotension, respiratory depression (Unal et al, 1994(Unal et al, , 1997Owen et al, 2000), and certain behavioral effects (Hirsch and O'Donohue, 1986) produced by morphine and ␤-endorphin 1-31 . The effect of glycyl-glutamine on place Fig.…”

Section: Discussionsupporting

confidence: 88%

“…The simple observation that Gly-Gln is synthesized with ␤-endorphin 1-27 , an opioid receptor antagonist, prompted us to investigate whether it might also influence the pharmacological effects of opioids. We found that Gly-Gln effectively inhibited the hypotension and respiratory depression caused by ␤-endorphin 1-31 or morphine, although it did not affect cardiovascular or respiratory function when given alone to otherwise untreated animals (Unal et al, 1994(Unal et al, , 1997Owen et al, 2000). By contrast, Gly-Gln had no effect at all on the antinociception evoked by opioids in the tail-flick and pawlift assays, even at doses over 100-fold higher than required to inhibit morphine-induced respiratory depression (Owen et al, 2000).…”

mentioning

confidence: 73%

“…By contrast, Gly-Gln had no effect at all on the antinociception evoked by opioids in the tail-flick and pawlift assays, even at doses over 100-fold higher than required to inhibit morphine-induced respiratory depression (Owen et al, 2000). This latter finding implies that Gly-Gln is unlikely to act as an opioid receptor antagonist, as ␤-endorphin 1-27 does, a conclusion supported by evidence from radioreceptor binding experiments (Unal et al, 1994). These data suggest that some POMC neurons release two peptides, ␤-endorphin 1-27 and Gly-Gln, capable of modulating the effects of ␤-endorphin 1-31 , albeit through different receptor mechanisms.…”

mentioning

confidence: 89%

“…instead of morphine (Table 1). The Gly-Gln stereoisomer glycyl-D-glutamine (Unal et al, 1994) also failed to influence the acquisition of a morphine place preference and was inactive when given alone to salinetreated control animals (Table 1). These data indicate that neither Gly-Gln hydrolysis nor nonspecific peptide effects are likely to explain the ability of Gly-Gln to inhibit acquisition of a morphine-conditioned place preference.…”

Section: Gly-gln Inhibitsmentioning

confidence: 99%

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Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

Çavun

Göktalay²,

Millington³

2005

J Pharmacol Exp Ther

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Glycyl-glutamine (Gly-Gln; ␤-endorphin [30][31] ) is an endogenous dipeptide synthesized from ␤-endorphin 1-31 . Previous investigations have shown that Gly-Gln inhibits the cardiovascular and respiratory depression caused by morphine and ␤-endorphin 1-31 , but it does not interfere with opioid analgesia. In this study, we tested whether Gly-Gln administration would influence morphine-induced conditioned place preference, tolerance, dependence, or withdrawal. For place preference experiments, rats were conditioned with morphine sulfate (2.5 mg/kg i.p.) or saline on alternate days for 6 days and tested on day 7. Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly. Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference, but it did not interfere with acquisition of a conditioned place preference to palatable food, and it did not produce place preference or aversion when given alone to morphine-naive animals. To induce antinociceptive tolerance, rats were treated with morphine (10 mg/kg i.p.) twice daily for 7 days, and morphine antinociception was evaluated with the tail-flick test. Glycylglutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly and partially reversed pre-established tolerance. Morphine dependence and withdrawal were assessed by measuring naloxone-precipitated withdrawal symptoms. Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.) and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone. Glycyl-glutamine thus attenuates morphine-induced conditioned place preference, tolerance, dependence, and withdrawal without compromising morphine analgesia.

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 73%

mentioning

confidence: 89%

Section: Gly-gln Inhibitsmentioning

confidence: 99%

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Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

Çavun

Göktalay²,

Millington³

2005

J Pharmacol Exp Ther

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“…GQ, an opioid-derived peptide, does not bind to opiate receptors, as shown by a NOVA screen. Further, displacement data shows GQ did not displace 3 H-naloxone from its receptors (Unal et al, 1994). Thus, GQ suppresses alcohol intake by a different mechanism than opiate receptor antagonists.…”

Section: Brain Site Selectionmentioning

confidence: 86%

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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Cloning and Characterization of the Gene Encoding the Mouse Peptide Transporter PEPT2

Rubio‐Aliaga

Boll

Daniel

2000

Biochemical and Biophysical Research Communications

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Beta-Endorphin-Induced Cardiorespiratory Depression is Inhibited by Glycyl-L-Glutamine, a Dipeptide Derived from Beta-Endorphin Processing. Appendix 1

Cited by 16 publications

References 32 publications

Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

Glycyl-Glutamine, an Endogenous β-Endorphin-Derived Peptide, Inhibits Morphine-Induced Conditioned Place Preference, Tolerance, Dependence, and Withdrawal

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

Cloning and Characterization of the Gene Encoding the Mouse Peptide Transporter PEPT2

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