PMID: 9166729Jun 1, 1997Paper

Chronic exposure to kappa-opioids enhances the susceptibility of immortalized neurons (F-11kappa 7) to apoptosis-inducing drugs by a mechanism that may involve ceramide

Journal of Neurochemistry
G DawsonR Goswami

Abstract

Chronic exposure of embryonic brain to opioids leads to microcephaly and developmental abnormalities. An immortalized mouse neuroblastoma x dorsal root ganglion hybrid cell line stably transfected to overexpress kappa-opioid receptors (F-11kappa7) showed complete loss of kappa-receptor binding to [3H]U69,593 after exposure to the kappa-agonist U69,593 for 24 h. U69,593 had no measurable effect on cell viability as determined by either cell viability or DNA fragmentation assays. However, when cell death (apoptosis) was induced by either staurosporine or the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002, cells pretreated with U69,593 for 24 h showed increased apoptosis compared with untreated cells. Thus, staurosporine (50 nM), wortmannin (4 microM), and LY294002 (30 microM) treatment for 24 h induced a 50% loss of cell viability and DNA fragmentation in 24 h. U69,593 pretreatment produced the same killing at lower concentrations, namely, 20 nM staurosporine, 2 microM wortmannin, and 14 microM LY294002, respectively. The effects of U69,593 were time-, dose-, and naloxone-reversible, suggesting that they are receptor-mediated. However, coaddition of U69,593 at the same time as staurosporine, wortmannin, or LY294...Continue Reading

Citations

Jan 5, 2000·Journal of Neurochemistry·P S Sastry, K S Rao
Oct 7, 2009·Annals of Plastic Surgery·Behtash Ghazi NezamiAhmad Reza Dehpour
Sep 14, 2012·Journal of Applied Toxicology : JAT·María José PolancoCarmen González-Martín
Mar 15, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·G Dawson
Nov 6, 2004·The International Journal of Neuroscience·Sebnem AticiUgur Oral
Nov 4, 2000·Journal of Neurotrauma·R E TomanA I Faden
Jan 13, 2005·Canadian Journal of Physiology and Pharmacology·Xin LinRui Wang
Nov 2, 2005·Neurotoxicity Research·K F HauserP E Knapp
Sep 1, 2005·Alcoholism, Clinical and Experimental Research·Mariko SaitoCsaba Vadasz
Mar 31, 2000·Journal of Neuroscience Research·R Goswami, G Dawson
May 30, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·G Anderson, M Maes
May 30, 2009·Toxicology Letters·Maria José PolancoCarmen González-Martín
Feb 16, 2010·Life Sciences·Armin Farajzadeh DeroeeAhmad Reza Dehpour
Nov 3, 2010·Best Practice & Research. Clinical Anaesthesiology·George K IstaphanousAndreas W Loepke

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis