Folic acid uptake by the human syncytiotrophoblast: interference by pharmacotherapy, drugs of abuse and pathological conditions.
Folic acid (FA) is crucial for fetal development. We aimed to study the modulation of FA placental uptake by: hyperserotoninemia and hyperglycaemia, anti-hypertensives, insulin and drugs of abuse. For this, we characterized (3)H-FA uptake by primary cultures of human cytotrophoblasts (TB cells) and tested the effects of these compounds upon (3)H-FA uptake, TB cell viability and gene expression. Our results show that: (a) acutely, (3)H-FA uptake was decreased by labetalol (0.1-1000 microM), ecstasy and amphetamine (0.025-25 microM); and (b) chronically, (3)H-FA uptake was decreased by high glucose (30 mM), atenolol, nicotine (0.1 and 10 microM), ethanol (0.01 and 10mM), ecstasy, amphetamine (0.25 and 1 microM) and tetrahydrocannabinol (1 and 100 nM). Moreover, many of these drugs were cytotoxic and they differentially modulated the mRNA expression of FA placental transport systems. Our results suggest that inhibition of FA placental uptake may constitute one of the mechanisms involved in the fetotoxicity of many of the compounds tested.
Keating
Elisa
E
Department of Biochemistry (U38/FCT), Faculty of Medicine, University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. keating@med.up.pt
Gonçalves
Pedro
P
Campos
Isabel
I
Costa
Fernanda
F
Martel
Fátima
F
D000661:Amphetamine / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology; D004461:Eclampsia / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D013287:Illicit Drugs / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D007741:Labetalol / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism*
D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D013287:Illicit Drugs; D007328:Insulin; D000431:Ethanol; D001262:Atenolol; D009538:Nicotine; D013759:Dronabinol; D005492:Folic Acid; D000661:Amphetamine; D005947:Glucose; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D007741:Labetalol