No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse.
Pharmacological approaches have defined the epsilon receptor as a beta-endorphin-preferring opioid receptor, described in rat vas deferens and in brain of several species. Only three opioid receptors-mu, delta and kappa-have been cloned and the existence of this additional subtype as a distinct protein remains controversial. Recently, the mouse brain epsilon receptor was detected in a G protein activation assay, as mediating residual beta-endorphin activity following pharmacological blockade of mu, delta and kappa receptors. To clarify whether this site is independent from mu, delta and kappa receptors, we performed beta-endorphin-induced [(35)S]GTPgammaS binding using mice lacking these three receptors (triple knockout mice). We tested both pons-medulla and whole brain preparations. beta-Endorphin strongly stimulated [(35)S]GTPgammaS binding in wild-type membranes but had no detectable effect in membranes from triple knockout mice. We conclude that the brain epsilon site involves mu, delta and/or kappa receptors, possibly coupled to nonclassical G proteins.
Contet
Candice
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP Parc d'innovation, 1 rue Laurent Fries BP 10142, C.U. de Strasbourg, 67404 Illkirch Cedex, France.
Matifas
Audrey
A
Kieffer
Brigitte L
BL
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000819:agonists; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011149:Pons / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000235:genetics; D001615:beta-Endorphin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C043460:epsilon receptor; D001615:beta-Endorphin; D019204:GTP-Binding Proteins