Overexpression of dynamin is induced by chronic stimulation of mu- but not delta-opioid receptors: relationships with mu-related morphine dependence.
Several studies using selective opioid agonists or mice with a deletion of the mu-opioid receptor, have shown that morphine dependence is essentially due to chronic stimulation of mu- but not delta-opioid receptors. Because dependence is assumed to be related to persistent intracellular modifications, we have investigated modifications putatively induced by chronic activation of mu receptors with morphine or selective agonists in vitro in SH-SY5Y cells and in vivo in different strains of mice, including mice lacking the mu-opioid receptor gene. The results show a similar down-regulation and desensitization of mu and delta binding sites, whereas an overexpression of dynamin occurred only with mu agonists, strongly suggesting the relevance of this up-regulation with the opiate dependence. Moreover, translocation of overexpressed dynamin from intracellular pools to plasma membranes was observed in chronic morphine-treated rats. This recruitment could be critically involved in long-lasting changes such as alterations of axonal transport observed in opioid dependence.
Noble
F
F
Département de Pharmacochimie Moléculaire et Structurale, Institut National de la Santé et de la Recherche Médicale U266, Université René Descartes, Unité de Formation et de Recherche, Paris, France.
Szücs
M
M
Kieffer
B
B
Roques
B P
BP
D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D034281:Dynamins; D005260:Female; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine; D020558:GTP Phosphohydrolases; D034281:Dynamins