Effects of Cannabinoids on Synaptic Membrane Enzymes. II. In vivo Studies of NaK-ATPase in Synaptic Membranes Isolated from Rat Brain

Abstract

Earlier work from this laboratory showed that Δ⁹-tetrahydrocannabinol (THC) from marijuana added in vitro to synaptic membranes from rat brain bound to the membranes and inhibited the NaK-ATPase (ATP phosphohydrolase, E.C. 3.6.1.3) enzyme system. The present study was carried out in vivo on the same enzyme. The dosages of THC given to the animals are less than the hypothermic dosages and in some instances are less than the dosages required to give the lethargic or anesthetic-like effects of THC when combined with alcohol. The dosages used in this study were 2 mg/kg in 10% ethanol in 5 ml of balanced salt solution (BSS), and 1 mg/kg in 5% ethanol in 5 ml of BSS. All percentage depressions of the NaK-ATPase in the rat synaptic membranes were calculated above the change brought about by ethanol alone. Inhibition was shown in this study to vary with the dosages of THC, and in all instances a high degree of inhibition was shown in the sodium pump activity of synaptic membranes at 20 minutes after THC administration to the rats. It is believed that these studies add to the present understanding of the effects of cannabinoids on human subjects in that the sodium pump activity at synaptic membranes is undoubtedly a dose-dependent phenomenon as are the observations of the effects of marijuana usage in humans.