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In Vitro and In Vivo Expression of Opioid and σ Receptors in Rat C6 Glioma and Mouse N18TG2 Neuroblastoma Cells
Author(s) -
Barg Jacob,
Thomas Gail E.,
Bem Wojciech T.,
Parnes Michael D.,
Ho Andrew M.,
Belcheva Mariana M.,
McHale Robert J.,
McLachlan Julie A.,
Tolman Kym C.,
Johnson Frank E.,
Coscia Carmine J.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63020570.x
Subject(s) - neuroblastoma , in vivo , sigma receptor , receptor , in vitro , opioid , glioma , opioid receptor , nude mouse , biology , sigma 1 receptor , microbiology and biotechnology , chemistry , cancer research , cell culture , biochemistry , agonist , genetics
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 [ 3 H][ d ‐Ala 2 , d ‐Leu 5 ]enkephalin and for σ 1 and σ 2 binding with 1,3‐[ 3 H]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 σ 1 binding of the neuroblastoma‐derived solid tumors became undetectable. In contrast, σ 2 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 σ 2 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.