Plasma membrane inhibition of macromolecular precursor transport by THC. |
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Authors: | B Desoize C Léger G Nahas |
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Institution: | 1. Faculté de Pharmacie, Laboratoire de Biochimie, 51, rue Cognacq-Jay, 51096 Reims Cedex, INSERM U-26, Laboratoire de Pharmacologie et de Toxicologie Cellulaires, 200, rue du Faubourg Saint-Denis, 75475 Paris Cedex 10-France;2. Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, N.Y., U.S.A. |
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Abstract: | 10?6to 10?4 M of delta-9-tetrahydrocannabinol (THC) or of other cannabinoids, which all have in common the C ring of olivetol, inhibit in cultured lymphocytes incorporation of 3H]thymidine. The inhibitory effect of olivetol derivatives is related to their octanol-water partition coefficient (liposolubility). Within 15 min of incubation, THC inhibits precursor pool formation and macromolecular incorporation of thymidine, uridine and leucine. THC inhibits also 14C] aminoisobutyric acid uptake into the cell, but does not alter the cellular “leakage” of this amino acid analogue. Using the isotopic dilution technique with L 1210 murine lymphoma cells and human lymphocytes, it was observed that THC decreases 3H]thymidine uptake within fifteen seconds after addition of the drug to the culture. Experiments performed at 0° indicate that THC has no action on thymidine binding to the carrier. All of these observations suggest that THC in micromolar concentration inhibits DNA synthesis through a “non-specific” alteration of membrane configuration. This effect, due to the liposolubility of the drug, could induce eonfonnational changes of membrane-bound transport systems which would inhibit their function. |
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