title: Beta-endorphin 1-31 biotransformation and cAMP modulation in inflammation.
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.
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Naghmeh Hajarol
authors.initials: NH
authors.lastname: Asvadi
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Herath M
authors.initials: HM
authors.lastname: Herath
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Amitha K
authors.initials: AK
authors.lastname: Hewavitharana
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: P Nicholas
authors.initials: PN
authors.lastname: Shaw
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cabot
mesh_terms: D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010455:Peptides / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D010455:Peptides; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D005576:Colforsin; D001615:beta-Endorphin; D000242:Cyclic AMP