Biochemical changes in rat testicular cells in Vitro produced by cannabinoids and alcohol: Metabolism and incorporation of labeled glucose, amino acids, and nucleic acid precursors

Abstract

The in vitro effects of Δ 9 -tetrahydrocannabinol (THC), various other water insoluble cannabinoids, and the water-soluble derivative of THC (SP-111A) on metabolism in testicular tissue slices and testicular cell suspensions were determined. Oxygen consumption and 14 CO 2 evolution were either unchanged or altered only slightly, but with [ 14 ]glucose, [ 14 C]leucine, [ 14 C]lysine, and [ 14 C]glycine as tracer substrates, cannabinoids at 0.1 m m caused significant diminution of the amount of radioactivity incorporated into nucleic acids, lipids, and proteins in testis slices. Cannabinoids at 0.1 m m also substantially inhibited both the synthesis of labeled nucleotides, especially di- and triphosphates, from labeled uridine, thymidine, or adenosine and the incorporation of radioactivity into nucleic acids. These effects of cannabinoids were enhanced in testicular spermatogenic cell suspensions as compared with testis slices, and SP-111A had marked effects even at 0.01 m m . Alcohol at 28 m m had either little or no effect. These results suggested that the decreased nucleic acid synthesis might be correlated with decreased concentrations of nucleotides. These reductions might be a consequence of decreased ATP or a direct effect of the cannabinoids on the kinases and/or polymerases involved. These inhibition of protein synthesis may in turn be a result of decreased nucleic acids and/or decreased energy levels.