Desipramine elicits the expression of opiate receptors and sulfogalactosylceramide synthesis in rat C6 glioma cells.
In the course of our studies on lipidoses induced by amphiphilic drugs, we have investigated the ef- of desipramine, a tricyclic antidepressant, on glial cells in culture. We noted that the addition of desipramine to the culture medium of C6 glioma cells resulted in the modification of the lipid profile of the cell membranes. Of particular interest was the presence, in the desipramine-treated cells, of an additional lipid comigrating on thin layer chromatography with sulfogalactosylceramide (S-GalCer). Addition of radiolabelled sulfuric acid in the culture medium of the desipramine-treated cells resulted in the incorporation of [35S]sulfate in the newly synthesized lipid. Furthermore, this lipid was localized selectively by indirect immunofluorescence using a specific rabbit anti-S-GalCer antibody on the cell surface of desipramine-treated, but not control, C6 cells. Desipramine also increased the activity of 3'-phosphoadenosine-5'-phosphosulfate sulfotransferase (the enzyme responsible for the synthesis of S-GalCer). Since it has been suggested that S-GalCer may be involved in opiate receptors, we looked for opiate binding sites on C6 glioma cells after exposure to desipramine. We found that dihydromorphine was able to bind to the desipramine-treated C6 cell membrane. The binding of [3H]dihydromorphine (180 fmol/mg protein) was stereospecific and had a KD of 30-60 nM. Furthermore, morphine reduced both the basal and isoproterenol-stimulated cyclic AMP levels of the desipramine-treated C6 cells. This effect was blocked by naloxone. In these respects, the opiate binding sites induced after treatment of C6 glioma cells with desipramine fulfill the requirements of a true opiate receptor.
D000818:Animals; D002554:Cerebrosides / Q000096:biosynthesis*; D003891:Desipramine / Q000494:pharmacology*; D004090:Dihydromorphine / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005699:Galactosylceramides / Q000096:biosynthesis*; D005910:Glioma / Q000378:metabolism*; D007700:Kinetics; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D002554:Cerebrosides; D005699:Galactosylceramides; D011957:Receptors, Opioid; D004090:Dihydromorphine; D003891:Desipramine