Iglesias Inmaculada, Albasanz Jose Luis, Martín Mairena
Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha , Ciudad Real, Spain .
Facultad de Ciencias y Tecnologías Químicas, Universidad de Castilla-La Mancha , Ciudad Real, Spain . ; Facultad de Medicina de Ciudad Real; Departamento de Química Inorgánica, Orgánica y Bioquímica, Universidad de Castilla-La Mancha , Ciudad Real, Spain .
J Caffeine Res. 2014 Dec 1;4(4):115-126. doi: 10.1089/jcr.2014.0010.
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 and A 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. In the present work, the effect of caffeine chronically consumed during pregnancy on A and A 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. Caffeine did not significantly alter AR neither at protein nor at gene expression level in both the maternal and fetal heart. On the contrary, AR significantly decreased in the maternal heart, although mRNA was not affected. Gi and Gs proteins were also preserved. Finally, AR-mediated inhibition of adenylyl cyclase activity did not change in the maternal heart, but AR mediated stimulation of this enzymatic activity significantly decreased according to the detected loss of this receptor. Opposite to the downregulation and desensitization of the AR/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, AR is downregulated and desensitized in the maternal heart, suggesting a differential modulation of these receptor-mediated pathways by caffeine.
咖啡因是世界上消费最为广泛的精神活性物质，即使在孕期也是如此。其刺激作用主要源于通过阻断腺苷A1和A2A受体来拮抗腺苷的作用。先前的研究表明，咖啡因能够穿过胎盘，因此不仅会调节胎儿大脑中的这些受体，还会调节心脏中的受体。在本研究中，利用放射性配体结合、蛋白质印迹法、腺苷酸环化酶活性测定以及逆转录聚合酶链反应，研究了孕期长期摄入咖啡因对Wistar大鼠母亲及其胎儿心脏中A1和A2A受体的影响。咖啡因在母体和胎儿心脏中，无论是在蛋白质水平还是基因表达水平上，均未显著改变A1受体。相反，母体心脏中的A2A受体显著减少，尽管mRNA未受影响。Gi和Gs蛋白也得以保留。最后，A1受体介导的腺苷酸环化酶活性抑制在母体心脏中未发生变化，但根据该受体的检测损失，A2A受体介导的该酶活性刺激显著降低。与先前报道的大脑中A2A受体/腺苷酸环化酶途径的下调和脱敏相反，这些结果表明，孕期咖啡因暴露后，该途径在大鼠心脏中未受影响。此外，母体心脏中的A2A受体下调且脱敏，这表明咖啡因对这些受体介导的途径具有差异性调节作用。
