Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the D9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes

The effects of cannabinoids on metabolic pathways and signal transduction systems were studied in primary cultures of rat astrocytes. D9-Tetrahydrocannabinol (THC), the major active component of marijuana, increased the rate of glucose oxida-tion to CO2 as well as the rate of glucose incorporation into phospholipids and glycogen. These effects of THC were mim-icked by the synthetic cannabinoid HU-210, and prevented by forskolin, pertussis toxin, and the CB1 receptor antagonist SR 141716. THC did not affect basal cAMP levels but partially antagonized the forskolin-induced elevation of intracellular cAMP concentration. THC stimulated p42/p44 mitogen-acti-vated protein kinase (MAPK) activity, Raf-1 phosphorylation, and Raf-1 translocation to the particulate cell fraction. In addi-tion, the MAPK inhibitor PD 098095 and the phosphoinositid