Effect of Cannabinoids upon the Uptake of Folic Acid by BeWo Cells

Abstract

Folic acid (FA) is an essential micronutrient that is particularly important during pregnancy for normal placental and fetal development and growth. The placenta and the fetus become frequently exposed to drugs of abuse such as cannabinoids because of maternal use of these substances. The aim of this study was to investigate the influence of cannabinoids on the uptake of FA by BeWo cells. Acute treatment with anandamide (1–10 μmol/l) caused a 15% decrease in ³H-FA uptake at pH 7.5. Moreover, tetrahydrocannabinol (THC) (1–10 μmol/l) caused a 30% increase, and AM630 (1 μmol/l) a 15% decrease in this parameter at pH 6.5. Neither the inhibitory effect of anandamide nor the stimulatory effect of THC were changed in the presence of cannabi- noid receptor type 1 or type 2 antagonists (AM251 and AM630, respectively). Chronic treatment (48 h) with THC (100 nmol/l) and AM251 (100 nmol/l) decreased the uptake of ³H-FA by 20% at pH 7.5, and anandamide (1 μmol/l) and AM630 (10–500 nmol/l) increased it by 30%. Moreover, CP55,940 (10 nmol/l) increased the uptake of ³H-FA by 30% at 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 (500 nmol/l). The mRNA levels of the proton-coupled folate transporter decreased by 17% and increased by 18% after chronic treatment with THC (0.1 μmol/l) and AM251 (100 nmol/l), respectively. In conclusion, ³H-FA uptake by BeWo cells is significantly, although not very markedly, changed by several distinct CB receptor agonists and antagonists, both after acute and chronic exposure of the cells. The acute effects of cannabinoid receptor agonists do not seem to be mediated by the cannabinoid receptor, and with a few exceptions the chronic effects do not seem to be related to changes in the expression levels of FA transporters.

Elevated homocysteine level in first-episode schizophrenia patients—the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse

“…These authors suggested that low folate level occurs most likely due to nutritional constraint. There are also studies showing that cannabinoids may impair the uptake of folate into BeWo cells (Araujo et al 2009) and human syncytiotrophoblasts (Keating et al 2009). However, the exact mechanism of this interaction remains unclear and requires further investigation.…”

Effect of oxygen concentrations on sodium iodide symporter expression and iodide uptake and hCG expression in human choriocarcinoma BeWo cells

“…BeWo cells form a well-differentiated monolayer, undergo syncytialization, and secrete hCG (8,35,58). They have been used widely in placental transport studies, e.g., glucose (1,3,6,13,25,38), amino acid (25,26,42), iron (12,18), fatty acid (24,60), and drug and toxic studies (2,22,36,47). BeWo cells express NIS and pendrin and demonstrate significant uptake and efflux of iodide, with kinetic and inhibitory characteristics consistent with these transporters (37).…”

Placental Transport of Thyroid Hormone and Iodide

“…They have been used widely in placental transport studies, e.g. glucose (Antony, et al 2007;Araujo, et al 2008;Baumann, et al 2007;Di Simone, et al 2009;Mark and Waddell 2006), amino acid (Jones, et al 2006a, b;Novak, et al 2006), iron (Danzeisen andMcArdle 1998;Gambling, et al 2001), fatty acid (Johnsen, et al 2009;Tobin, et al 2009), and drug and toxicity studies (Araujo, et al 2009;Hirano, et al 2008;Magnarin, et al 2008;Prouillac, et al 2009). BeWo cells express both of the iodide transporters, NIS and Pendrin (Manley et al 2005).…”