title: Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain.
abstract: The Fas receptor is involved in the regulation of apoptosis but also can function as a non-apoptotic signal transducer. This study was mainly designed to quantitate Fas proteins in rat brain during heroin addiction and opiate withdrawal. In rat, mouse and human brains, and in SH-SY5Y cells, similar forms of Fas were immunodetected with different antibodies (i.e., 35 kDa native Fas and 48- and 51-kDa glycosylated Fas). Acute (2 h) treatments with the micro-opioid receptor agonists heroin (10 mg/kg) and morphine (30 mg/kg) increased the immunodensity of native Fas (124% and 36%) but not that of glycosylated Fas in the cerebral cortex. Chronic (5 days) heroin (5-30 mg/kg) and morphine (10-100 mg/kg) were also associated with increased native Fas (76% and 45%) and with different expressions of glycosylated Fas. In heroin-dependent rats, opiate withdrawal (48 h) resulted in a sustained increase in native Fas (107%) and in up-regulation of 51 kDa glycosylated Fas (51%). Acute treatments with selective delta-receptor (SNC-80, 10 mg/kg) or kappa-receptor (U 50488-H, 10 mg/kg) agonists did not alter the content of native or glycosylated Fas. Chronic pentazocine (10-80 mg/kg, 5 days), a mixed opiate drug and sigma(1) receptor agonist, decreased native (48%) and glycosylated (38-82%) Fas proteins. Similarly, the selective sigma(1) agonist (+)-SKF 10047 also decreased native Fas (37%) and the effect was blocked by the sigma(1) antagonist BD 1063. Brain dynamin was up-regulated by acute and/or chronic heroin (30-39%), morphine (47-85%), pentazocine (51%) and heroin withdrawal (74%). The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35 kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brain.
authors.affiliation: Laboratory of Neuropharmacology, Associate Unit of the Institute of Neurobiology "Ramón y Cajal" (CSIC), Department of Biology, University of the Balearic Islands, Cra. Valldemossa Km 7.5, 07122, Palma de Mallorca, Spain.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: García-Fuster
authors.forename: Marcel
authors.initials: M
authors.lastname: Ferrer-Alcón
authors.forename: Antonio
authors.initials: A
authors.lastname: Miralles
authors.forename: Jesús A
authors.initials: JA
authors.lastname: García-Sevilla
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D003932:Heroin / Q000009:adverse effects / Q000494:pharmacology; D066298:In Vitro Techniques; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000378:metabolism*; D010423:Pentazocine / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000819:agonists; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D017480:Receptors, sigma; D019014:fas Receptor; D003932:Heroin; D009020:Morphine; D034281:Dynamins; D010423:Pentazocine