Modulation of folic acid uptake into BeWo cells by cannabinoids

Abstract

The aim of this study was to investigate the influence of cannabinoids (CB) on the uptake of folic acid (FA) by the choriocarcinoma cell line (BeWo cells). Acutely, anandamide caused a 15% decrease in 3H‐FA uptake (pH 7.5). Moreover, tetrahydrocannabinol (THC) caused a 30% increase, and AM630 a 15% decrease (pH 6.5). Neither the inhibitory effect of anandamide nor the stimulatory effect of THC were changed by the CB receptor type 1 or type 2 antagonists (AM251 and AM630, respectively). Chronically (48 h), THC and AM251 decreased by 20% the uptake of 3H‐FA, and anandamide and AM630 increased it by 30% (pH 7.5). Moreover, CP 55,940 increased uptake of 3H‐FA by 30% (pH 6.5). RT‐PCR analysis showed that the mRNA levels of the Reduced Folate Transporter 1 increased by 9% after chronic treatment with AM630, and the mRNA levels of the Proton‐coupled Folate Transporter decreased by 17% and increased by 18% after chronic treatment with THC and AM251, respectively. In conclusion, uptake of 3H‐FA by BeWo cells is significantly, although not very markedly, changed by several distinct CB receptor agonists and antagonists, either after acute and after chronic exposure of the cells. The acute effects of CB receptor agonists do not seem to be CB receptor‐mediated, and with a few exceptions the chronic effects do not seem to be related to changes in the expression levels of FA transporters.Supported by FCT (PTDC/SAU‐FCF/67805/2006)