A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine-induced opioid binding sites on rat C6 glioma cells and attenuates thymidine incorporation into DNA.
Treatment of rat C6 glioma cells with the tricyclic antidepressant desipramine induces opioid binding. Here the distribution of these opioid-binding sites on C6 cell membranes and a functional property were investigated. Immunohistochemical examination of C6 cells was performed using a monoclonal anti-idiotypic antibody to opioid receptors (Ab2AOR). Ab2AOR uniformly labeled > 97% of the cells exposed to desipramine over their entire surface. The opioid-receptor antagonist naltrexone completely blocked Ab2AOR binding. Ab2AOR, which has opioid agonist properties, also inhibited DNA synthesis in desipramine-treated but not in naive C6 cells. Similarly, morphine blocked C6 cell proliferation only after desipramine treatment. The antineurotrophic action of Ab2AOR was reversed by naltrexone and was insensitive to pertussis toxin. These findings demonstrate that Ab2AOR suppresses the proliferation of C6 glioma cells by binding to desipramine-induced opioid receptors.
Barg
J
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Belcheva
M M
MM
Levy
R
R
McHale
R J
RJ
McLachlan
J A
JA
Johnson
F E
FE
Coscia
C J
CJ
Vogel
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001932:Brain Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003124:Colorimetry; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D003720:Densitometry; D003891:Desipramine / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism*; D007150:Immunohistochemistry; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D009271:Naltrexone; D009020:Morphine; D037342:Pertussis Toxin; D003891:Desipramine; D013936:Thymidine