Identification of morphine-6-glucuronide in chromaffin cell secretory granules.
Fiche publication
Date publication
mars 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VAN DORSSELAER Alain, Dr CHASSEROT-GOLAZ Sylvette, Dr GOUMON Yannick, Pr ROHR Olivier
Tous les auteurs :
Goumon Y, Muller A, Glattard E, Marban C, Gasnier C, Strub JM, Chasserot-Golaz S, Rohr O, Stefano GB, Welters ID, Van Dorsselaer A, Schoentgen F, Aunis D, Metz-Boutigue MH
Lien Pubmed
Résumé
We report for the first time that morphine-6-glucuronide, a highly analgesic morphine-derived molecule, is present in adrenal chromaffin granules and secreted from chromaffin cells upon stimulation. We also demonstrate that phosphatidylethanolamine-binding protein (alternatively named Raf-1 kinase inhibitor protein or RKIP) acts as an endogenous morphine-6-glucuronide-binding protein. An UDP-glucuronosyltransferase 2B-like enzyme, described to transform morphine into morphine-6-glucuronide, has been immunodetected in the chromaffin granule matrix, and morphine-6-glucuronide de novo synthesis has been characterized, demonstrating the possible involvement of intragranular UDP-glucuronosyltransferase 2B-like enzyme in morphine-6-glucuronide metabolism. Once secreted into the circulation, morphine-6-glucuronide may mediate several systemic actions (e.g. on immune cells) based on its affinity for mu-opioid receptors. These activities could be facilitated by phosphatidylethanolamine-binding protein (PEBP), acting as a molecular shield and preventing morphine-6-glucuronide from rapid clearance. Taken together, our data represent an important observation on the role of morphine-6-glucuronide as a new endocrine factor.
Référence
J Biol Chem. 2006 Mar 24;281(12):8082-9