Effect of Caffeine Chronically Consumed During Pregnancy on Adenosine A₁ and A_2A Receptors Signaling in Both Maternal and Fetal Heart from Wistar Rats

Abstract

Background: Caffeine is the most widely consumed psychoactive substance in the world, even during pregnancy. Its stimulatory effects are mainly due to antagonism of adenosine actions by blocking adenosine A 1 and A 2A receptors. Previous studies have shown that caffeine can cross the placenta and therefore modulate these receptors not only in the fetal brain but also in the heart. Methods: In the present work, the effect of caffeine chronically consumed during pregnancy on A 1 and A 2A receptors in Wistar rat heart, from both mothers and their fetuses, were studied using radioligand binding, Western-blotting, and adenylyl cyclase activity assays, as well as reverse transcription polymerase chain reaction. Results: Caffeine did not significantly alter A 1 R neither at protein nor at gene expression level in both the maternal and fetal heart. On the contrary, A 2A R significantly decreased in the maternal heart, although mRNA was not affected. Gi and Gs proteins were also preserved. Finally, A 1 R-mediated inhibition of adenylyl cyclase activity did not change in the maternal heart, but A 2A R mediated stimulation of this enzymatic activity significantly decreased according to the detected loss of this receptor. Conclusions: Opposite to the downregulation and desensitization of the A 1 R/AC pathway previously reported in the brain, these results show that this pathway is not affected in rat heart after caffeine exposure during pregnancy. In addition, A 2A R is downregulated and desensitized in the maternal heart, suggesting a differential modulation of these receptor-mediated pathways by caffeine.

Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy

“…Importantly, the expression of receptors that mediate Ado actions may vary in response to various stimuli or may be under circadian variations. One of the best known examples is the regulation of AR expression in response to caffeine intake [ 22 , 23 ]. Taking the kidney as a model, the expression of the four ARs happens to be heterogeneous when considering the different anatomical regions [ 24 , 25 , 26 , 27 ]; even in a single renal tubular epithelial cell, the expression may be fairly different in the basolateral and luminal membranes [ 28 , 29 ].…”