The use of brain slices for the study of enzymatic metabolism of Des-enkephalin-tau-endorphin (DEtauE) and its analogues.

Persistent Link:
http://hdl.handle.net/10150/144671
Title:
The use of brain slices for the study of enzymatic metabolism of Des-enkephalin-tau-endorphin (DEtauE) and its analogues.
Author:
Li, Zhiwei.
Issue Date:
1989
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The present study utilized a newly developed rat brain slice and incubation techniques to determine the effects of peptide structural modifications and brain peptidase regional specificity on neuropeptide metabolism. Organon (Oss, The Netherlands) provided us with a series of $\tau$-endorphin analogues with structural and conformational changes. Differences between the half-lives of the endogenous peptide Des-enkephalin-$\tau$-endorphin (DE$\tau$E) and its analogues were estimated after time-course incubations with discrete, regionally dissected rat brain slices. Tissue viability was estimated as the ability of the slice to uptake ($\sp3$H) -GABA, or to release ($\sp3$H) -GABA following K$\sp+$ stimulation. Results demonstrated stability of uptake/release up to 5 hours of incubation, suggesting tissue viability over this period. Our results suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. Changes in DE$\tau$E structure (Pro$\sp7$ substitution, and Lys$\sp9$ acetylation) appear to increase the half-life of DE$\tau$E. However, cyclization of DE$\tau$E, and substitutions with D-Thr and cyclohexylalanine did not appear to result in an increase in peptide half-life in the brain regions tested. In summary, these studies have shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of the rat brain.
Type:
text; Thesis-Reproduction (electronic)
LCSH Subjects:
Endorphins - Metabolism; Neuropeptides - Metabolism; Pharmacology
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Davis, Thomas P.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe use of brain slices for the study of enzymatic metabolism of Des-enkephalin-tau-endorphin (DEtauE) and its analogues.en_US
dc.creatorLi, Zhiwei.en_US
dc.contributor.authorLi, Zhiwei.en_US
dc.date.issued1989en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe present study utilized a newly developed rat brain slice and incubation techniques to determine the effects of peptide structural modifications and brain peptidase regional specificity on neuropeptide metabolism. Organon (Oss, The Netherlands) provided us with a series of $\tau$-endorphin analogues with structural and conformational changes. Differences between the half-lives of the endogenous peptide Des-enkephalin-$\tau$-endorphin (DE$\tau$E) and its analogues were estimated after time-course incubations with discrete, regionally dissected rat brain slices. Tissue viability was estimated as the ability of the slice to uptake ($\sp3$H) -GABA, or to release ($\sp3$H) -GABA following K$\sp+$ stimulation. Results demonstrated stability of uptake/release up to 5 hours of incubation, suggesting tissue viability over this period. Our results suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. Changes in DE$\tau$E structure (Pro$\sp7$ substitution, and Lys$\sp9$ acetylation) appear to increase the half-life of DE$\tau$E. However, cyclization of DE$\tau$E, and substitutions with D-Thr and cyclohexylalanine did not appear to result in an increase in peptide half-life in the brain regions tested. In summary, these studies have shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of the rat brain.en_US
dc.typetexten_US
dc.typeThesis-Reproduction (electronic)en_US
dc.subject.lcshEndorphins - Metabolismen_US
dc.subject.lcshNeuropeptides - Metabolismen_US
dc.subject.lcshPharmacologyen_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairDavis, Thomas P.en_US
dc.contributor.committeememberBrendel, Klausen_US
dc.contributor.committeememberBurks, Thomas F.en_US
dc.contributor.committeememberPorreca, Franken_US
dc.identifier.proquest1337480en_US
dc.identifier.oclc708392783en_US
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