Delta9-tetrahydrocannabinol stimulates glucose utilization in C6 glioma cells.
The present work was undertaken to study the metabolic response of C6 glioma cells to physiologically relevant doses of delta9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC produced a dose-dependent increase in the rates of glucose oxidation to CO2 and glucose incorporation into phospholipids and glycogen. The THC-induced stimulation of glucose utilization was (i) dose-dependent up to 100 nM THC, (ii) mimicked by the synthetic cannabinoid HU-210, and (iii) prevented by pertussis toxin and the CB1 receptor antagonist SR141716A. In contrast to THC, forskolin markedly depressed CO2 production, phospholipid synthesis and glycogen synthesis from glucose. The forskolin-induced inhibition of glucose utilization was (i) mimicked by dibutyryl-cAMP, and (ii) prevented by THC, HU-210 and H-7, an inhibitor of the cAMP-dependent protein kinase. Likewise, THC was able to antagonize in part the forskolin-induced elevation of intracellular cAMP concentration, and this antagonistic effect was prevented by SR141716A. However, THC per se did not affect basal cAMP concentration. Results thus indicate that physiologically relevant doses of THC stimulate glucose metabolism in C6 glioma cells through a cannabinoid receptor-mediated process. Although cannabinoid receptors may be coupled to inhibition of adenylyl cyclase in C6 glioma cells, this does not seem to be the mechanism involved in the THC-induced stimulation of glucose metabolism.
Sánchez
C
C
Department of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University, Madrid, Spain.
Velasco
G
G
Guzmán
M
M
D013759:Dronabinol / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D010743:Phospholipids; D013759:Dronabinol; D006003:Glycogen; D005947:Glucose