In Vitro and In Vivo Expression of Opioid and σ Receptors in Rat C6 Glioma and Mouse N18TG2 Neuroblastoma Cells |
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Authors: | †Jacob Barg ‡Gail E Thomas ‡Wojciech T Bem ‡Michael D Parnes Andrew M Ho Mariana M Belcheva Robert J McHale ‡Julie A McLachlan Kym C Tolman ‡Frank E Johnson Carmine J Coscia |
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Institution: | E. A. Doisy Department of Biochemistry and Molecular Biology and; Department of Surgery, St. Louis University School of Medicine, St. Louis, Missouri, U.S.A.;and; Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel |
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Abstract: | Abstract: Mouse N18TG2 neuroblastoma and rat C6 glioma cell lines were injected into male nude mice, and the tumors were passaged serially. At each generation, tumors were analyzed for δ opioid binding using 3H] d -Ala2, d -Leu5]enkephalin and for σ1 and σ2 binding with 1,3-3H]di- o -tolylguanidine in the presence and absence of 1 µ M pentazocine. Receptor density ( B max) and affinity ( K D) were estimated by homologous competition binding assays. Opioid and σ B max values in the solid tumors were significantly lower than their original levels in vitro. K D values for opioid/σ ligands were similar in vitro and in vivo. With successive passages in the murine host, δ opioid and σ1 binding of the neuroblastoma-derived solid tumors became undetectable. In contrast, σ2 receptor B max values were unchanged with successive passages of the neuroblastoma-derived tumors and doubled in the nude mouse-borne gliomas. When neuroblastoma-derived solid tumors that were devoid of δ opioid binding were returned to culture, opioid receptors appeared to be up-regulated as compared with their original in vitro levels. Serial passaging of these recultured cells in vivo again resulted in a rapid decline in opioid receptor content. The opioid data are consistent with our prior findings on opioid binding diminution in human brain tumors. The pattern of change for σ binding was more complex, with the σ2 response in late passages of the glioma being reminiscent of the formerly observed increase in number of σ sites in transformed human meninges, kidney, and colon tissue. |
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Keywords: | Opioid receptors σ receptors Neuroblastoma Glioma Nude mice |
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