Effect of glutamate intake during gestation on adenosine A(1) receptor/adenylyl cyclase pathway in both maternal and fetal rat brain |
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Authors: | León David Albasanz José Luis Castillo Carlos Alberto Martín Mairena |
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Affiliation: | Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain |
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Abstract: | Pregnant Wistar rats were orally treated with 1 g/L l -glutamate during the entire gestational period and the status of adenosine A1 receptor (A1R)/adenylyl cyclase transduction pathway from maternal and fetal brain was analyzed. Glutamate consumption, estimated from the loss of water from the drinking bottles, was 110 ± 4.6 mg/kg/day. In mother brains glutamate intake did not significantly alter the B max value, although the K d value was significantly decreased. However in fetus brain, a significant decrease in B max was observed, without an alteration of K d value. Similar results were observed by western blot assays using specific A1R antibody, suggesting a down-regulation of A1R in fetal brain. Concerning α subunits of inhibitory G proteins (Gi), αGi3 protein was slightly but significantly decreased in maternal brain without alterations of either Gi1 or Gi2. In contrast, αGi1 and αGi2 isoforms were increased in fetal brain. On the other hand, basal, forskolin, and forskolin plus GTPγS-stimulated adenylyl cyclase activity was significantly decreased in both maternal and fetal brain, and this was more prominent in fetal than in maternal brain. Finally, A1R functionality was significantly decreased in mother brain whereas no significant differences were detected in fetus brain. These results suggest that glutamate administered to pregnant rats modulates A1R signaling pathways in both tissues, showing an A1R down-regulation in fetal brain, and desensitization in maternal brain. |
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Keywords: | adenosine A1 receptors cross-talk glutamate receptors l-glutamate pregnancy |
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