Effect of delta-9-tetrahydrocannabinol on the in vitro uptake of alpha-amino isobutyric acid by term human placental slices.
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 alpha-amino isobutyric acid was inhibited in a dose-dependent fashion, correlating with the log of the dose (1-100 microM THC; r = 0.945; p less than 0.01). Compared to control tissue, significant impairment of alpha-amino isobutyric acid uptake began at 20 microM THC. Similar results were found for valine. The time course (30-120 min) for alpha-amino isobutyric acid uptake showed linearity for both control and THC-(50 microM) treated tissue, but there was a marked reduction in the THC slope. Uptake of alpha-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 microM 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 microM THC = 26.96 +/- 6.22 (mmol/liter intracellular water per h) (p less than 0.01); and no change in diffusion constant (Km): control Km = 0.78 +/- 0.08 versus 50 microM THC = 0.80 +/- 0.09 (mM).(ABSTRACT TRUNCATED AT 250 WORDS)
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008854:Microscopy, Electron; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000621:Aminoisobutyric Acids; C100049:2-aminoisobutyric acid; D013759:Dronabinol