Chronic intake of caffeine during gestation down regulates metabotropic glutamate receptors in maternal and fetal rat heart

Abstract

Caffeine is the most widely consumed substance in the world which antagonizes adenosine effects. Adenosine acting through A(1) receptors inhibits glutamate release which binds to metabotropic glutamate receptors (mGluRs). Recently, we have shown that maternal caffeine intake during gestation causes down-regulation of A(1) and metabotropic glutamate receptors in the brain of both rat mothers and fetuses. In the present work we provide evidence that caffeine also affects receptors in hearts, causing a decrease in mGluRs from both maternal and fetal hearts. A decrease in G(q/11) and PLC beta(1) proteins level was also observed in both tissues. However, phospholipase C activity was only affected in fetal heart, being significantly decreased. These results suggest an in vivo cross-talk mechanism between adenosine and glutamate receptors in peripheral tissues. Therefore, special attention should be paid to caffeine ingestion during gestation.

Exciting Times beyond the Brain: Metabotropic Glutamate Receptors in Peripheral and Non-Neural Tissues

“…In the human heart, mGlu receptors 1 and 5 but not mGlu2/3 were found in atrial intramural ganglia, atrial and ventricular cardiocytes, and bundle of Hiss (Gill et al, 2007). In addition, the components of mGlu/PLC pathway have been studied in the pregnant rat heart (Iglesias et al, 2006). It is noteworthy that maternal intake of caffeine during rat gestation causes downregulation of mGlu1 protein level in the fetus heart and a loss of responsivity to several mGlu receptor agonists in membrane preparations isolated from the heart of the fetus (Iglesias et al, 2006).…”

The effects of prenatal exposure to methylxanthines

“…Adenosine is a nucleoside distributed in the heart and involved in cardiovascular response (Flood et al 2002, Xu et al 2005, Iglesias et al 2006). Hence, caffeine as a nonselective adenosine antagonist is expected to influence cardiovascular system.…”

“…Metabotropic glutamate receptors have been proved to be present in the heart and play a role in its physiology (Us et al 2001, Iglesias et al 2006. Recently, (Iglesias et al 2006) have demonstrated down-regulation of mGluRs and a decrease in Gq/11 and PLCβ proteins in fetal rat hearts exposed to caffeine via maternal intake.…”

“…Recently, (Iglesias et al 2006) have demonstrated down-regulation of mGluRs and a decrease in Gq/11 and PLCβ proteins in fetal rat hearts exposed to caffeine via maternal intake. No changes in mRNA level have been identified, hence these results suggest the involvement of post-transcriptional mechanisms.…”

“…They are mainly absorbed from coffee, tea and cocoa products such as cola beverages and chocolate bars, as well as some medications. Methylxanthines have been demonstrated to exhibit multifunctional physiological effects mediated proved to be the main target for methylxanthines (Iglesias et al 2006). Gil et al (1993) reported an inhibitory effect of purinergic receptor antagonists suramin and theobromine on angiogenesis induced in mice by lung cancer cells.…”