Abstract |
Glycyl-L-glutamine ( Gly-Gln; beta-endorphin 30-31) is an endogenous dipeptide that is synthesized through the post-translational processing of beta-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central beta-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with beta-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of beta-endorphin- induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. beta-endorphin, consistent with evidence that cyclic dipeptides permeate the blood-brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by beta-endorphin or morphine.
|
Authors | C B Unal, M D Owen, W R Millington |
Journal | Brain research
(Brain Res)
Vol. 747
Issue 1
Pg. 52-9
(Jan 30 1997)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 9042527
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Narcotic Antagonists
- Narcotics
- beta-Endorphin
- Morphine
|
Topics |
- Animals
- Blood Pressure
(drug effects)
- Depression, Chemical
- Dose-Response Relationship, Drug
- Heart Rate
(drug effects)
- Hemodynamics
(drug effects)
- Injections, Intra-Arterial
- Injections, Intraventricular
- Male
- Morphine
(administration & dosage, antagonists & inhibitors, pharmacology)
- Narcotic Antagonists
(administration & dosage, pharmacology)
- Narcotics
(administration & dosage, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Respiratory Insufficiency
(chemically induced, prevention & control)
- Respiratory Mechanics
(drug effects)
- beta-Endorphin
(administration & dosage, antagonists & inhibitors, pharmacology)
|