Adenosine A1 receptor down-regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats.
Pregnant rats were treated daily with 1 g/L of caffeine or theophylline in their drinking water during pregnancy and the effect of these methylxanthines on adenosine A1 receptor was assayed using binding and reverse transcription polymerase chain reaction (RT-PCR) assays in brains from both mothers and full-term fetuses. In plasma membranes from pregnant rat brain, caffeine and theophylline caused a significant decrease in total receptor numbers, of the same order in both cases (30%), with no significant changes on receptor affinity. The effect of these adenosine receptor antagonists on plasma membranes from fetal brains was more marked, being detected at approximately 50% of the total receptors detected in control conditions. However, in this tissue, a significant increase in the receptor affinity, of the same order in both cases, was also detected after antagonist administration. No significant variation on the potency of caffeine and theophylline as antagonists was detected after treatments in mothers; however, higher affinities were detected in fetuses. A decrease in the total receptor numbers in fetal brain was associated with an increase in the mRNA coding A1 receptor, as determined by RT-PCR assays, not having detected any mRNA difference in maternal brain. No variation in the levels of mRNA coding A2A receptor was detected in any case. These results suggest that maternal caffeine or theophylline intake modulates adenosine A1 receptor, causing a down-regulation of adenosine A1 receptor in brain in both mothers and fetuses.
León
David
D
Area de Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha,Ciudad Real, Spain.
Albasanz
José Luis
JL
Ruíz
María Angeles
MA
Fernández
Mercedes
M
Martín
Mairena
M
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D011247:Pregnancy; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013806:Theophylline / Q000494:pharmacology*; D014316:Tritium; D014970:Xanthines / Q000493:pharmacokinetics
D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014316:Tritium; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline