Chronic caffeine or theophylline intake during pregnancy inhibits A1 receptor function in the rat brain

The aim of this work was to study whether caffeine or theophylline chronically consumed during pregnancy affect inhibitory adenylyl cyclase pathway mediated by adenosine, in rat brain of both mothers and full-term fetuses. Immunoblotting analysis revealed a significant decrease in αGi1,2 subunit level (27-29% in mothers, 15-18% in fetuses), associated with a significant increase in the mRNA level coding αGi1 in both maternal and fetal rat brain (12-22%) after methylxanthine intake. No significant differences in αGi3 level were detected in any case. On the other hand, forskolin- and forskolin plus guanosine-5′-O(3-thiotriphosphate) tetralithium salt-stimulated adenylyl cyclase activity was significantly decreased (30-36%) in maternal brain. Moreover, adenylyl cyclase inhibition elicited by N6-cyclohexyladenosine, specific adenosine A1 receptor agonist, was also significantly decreased in caffeine- (40.5%) and theophylline- (55.0%) treated mothers, suggesting a desensitization of adenosine A1 receptor/adenylyl cyclase pathway in maternal brain. However, no significant differences were detected in fetal brain between control and treated animals. Therefore, caffeine or theophylline chronic intake during pregnancy differently modulates inhibitory adenylyl cyclase pathway mediated by adenosine in maternal and fetal brain causing a loss of the system responsiveness only in maternal brain but down-regulating Gi1 protein in both mother and fetus brain.