Beta-Endorphin 1-31 Biotransformation and cAMP Modulation in Inflammation

Asvadi, Naghmeh Hajarol, Morgan, Michael, Herath, Herath M., Hewavitharana, Amitha K., Shaw, P. Nicholas and Cabot, Peter J. (2014) Beta-Endorphin 1-31 Biotransformation and cAMP Modulation in Inflammation. PLoS One, 9 3: e90380.1-e90380.11. doi:10.1371/journal.pone.0090380


Author Asvadi, Naghmeh Hajarol
Morgan, Michael
Herath, Herath M.
Hewavitharana, Amitha K.
Shaw, P. Nicholas
Cabot, Peter J.
Title Beta-Endorphin 1-31 Biotransformation and cAMP Modulation in Inflammation
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0090380
Open Access Status DOI
Volume 9
Issue 3
Start page e90380.1
End page e90380.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract A large body of evidence now exists for the immune cell expression, production, and the release of beta-endorphin (BE 1-31) within inflamed tissue. The inflammatory milieu is characterised by increased acidity, temperature and metabolic activity. Within these harsh conditions BE 1-31 is even more susceptible to increased enzymatic degradation over that of plasma or other non-injured tissue. To elucidate the biotransformation pathways of BE 1-31 and provide an insight to the impact of inflamed tissue environments, BE 1-31 and three of its major N-terminal fragments (BE 1-11, BE 1-13 and BE 1-17) were incubated in inflamed tissue homogenates at pH 5.5 for 2 hrs. In addition, the potency of BE 1-31 and five main N - terminal fragments (BE 1-9, BE 1-11, BE 1-13, BE 1-17, BE 1-20) was assessed at mu-opioid receptors (MOR), delta-opioid receptors (DOR), and kappa-opioid receptors (KOR). Opioid receptor potency was investigated by examining the modulation of forskolin induced cAMP accumulation. The majority of the N-terminal fragment of BE 1-31 had similar efficacy to BE 1-31 at MOR. The shortest of the major N-terminal fragments (BE 1-9), had partial agonist activity at MOR but possessed the highest potency of all tested peptides at DOR. There was limited effect for BE 1-31 and the biotransformed peptides at KOR. Major N-terminal fragments produced within inflamed tissue have increased presence within inflamed tissue over that of the parent molecule BE 1-31 and may therefore contribute to BE 1-31 efficacy within disease states that involve inflammation.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Pharmacy Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 01 Apr 2014, 20:01:41 EST by Charna Kovacevic on behalf of School of Pharmacy