Adenosine A₁ receptor down‐regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats

Abstract

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 A 1 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 A 1 receptor, as determined by RT-PCR assays, not having detected any mRNA difference in maternal brain. No variation in the levels of mRNA coding A 2A receptor was detected in any case. These results suggest that maternal caffeine or theophylline intake modulates adenosine A 1 receptor, causing a downregulation of adenosine A 1 receptor in brain in both mothers and fetuses.

Differential Effect of Caffeine Consumption on Diverse Brain Areas of Pregnant Rats

“…Nine control pregnant rats received drug-free tap water. As we previously reported, 23 daily water intake and rat weight during the gestational period were of the same order in the two animal groups (pregnant rats not treated and treated with caffeine).…”

Caffeine effects on AdoR mRNA expression in Drosophila melanogaster

“…A high concentration of adenosine in hemolymph can lead to the degeneration of the fat body, hemocyte apoptosis and imaginal disc deformation [20]. Therefore, long-term ADA inhibition through persistent exposure to caffeine may cause a deregulation of the adenosine metabolism, which could disrupt the cell metabolism and subsequently could affect AdoR expression [12,43].…”

Caffeine Intake during Pregnancy: What Are the Real Evidences?

“…As the fetus is unable to metabolize it properly, it is exposed to the same level of caffeine ingested by the mother [8,18,30].…”