Effect of -∆9-tetrahydrocannabinol on the in vitro uptake of α-amino isobutyric acid by term human placental slices

Abstract

Tetrahydrocannabinol (THC), the active component in marijuana smoke, crosses the placenta and is a potential fetotoxic agent. In both human and animal studies, the most consistent fetal effect of THC is intrauterine growth retardation. Since fetal somatic growth is dependent on placental transfer of nutrients, including essential amino acids, we studied the effect of THC upon the in vitro uptake of amino acid by term human placental slices. Uptake of α-amino isobutyric acid was inhibited in a dose-dependent fashion, correlating with the log of the dose (1-100 μM THC; r = 0.945; p < 0.01). Compared to control tissue, significant impairment of a-amino isobutyric acid uptake began at 20 μM THC. Similar results were found for valine. The time course (30-120 min) for μ-amino isobutyric acid uptake showed linearity for both control and THC- (50 μM) treated tissue, but there was a marked reduction in the THC slope. Uptake of α-amino isobutyric acid was significantly reduced at all times. The sustained effect of THC was slightly, but significantly, reversed by removal of THC from the medium after 90 min of 50 μM THC exposure. Only partial reversal may have been due to the 15- to 20-fold accumulation of THC in the placental tissue. Uptake kinetics showed noncompetitive inhibition with decreased Vmax: control Vmax = 51.66 ± 6.26 versus 50 μM THC = 26.96 ± 6.22 (mmol/ liter intracellular water per h) (p < 0.01); and no change in diffusion constant (Km): control Km = 0.78 ± 0.08 versus 50 μM THC = 0.80 ± 0.09 (mM). In addition, 50 μM THC caused a modest increase in Kd, but the difference was not significant: control Kd = 3.82 ± 0.29 versus 50 μM THC = 5.19 ± 1.03 (h-l). Using actively transported amino acids as an index, the results of these experiments suggest that THC may be placento-toxic. © 1987 International Pediatric Research Foundation, Inc.