Effect of glutamate intake during gestation on adenosine A(1) receptor/adenylyl cyclase pathway in both maternal and fetal rat brain.
Pregnant Wistar rats were orally treated with 1 g/L l-glutamate during the entire gestational period and the status of adenosine A(1) receptor (A(1)R)/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 A(1)R antibody, suggesting a down-regulation of A(1)R in fetal brain. Concerning alpha subunits of inhibitory G proteins (Gi), alphaGi(3) protein was slightly but significantly decreased in maternal brain without alterations of either Gi(1) or Gi(2). In contrast, alphaGi(1) and alphaGi(2) isoforms were increased in fetal brain. On the other hand, basal, forskolin, and forskolin plus GTPgammaS-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, A(1)R 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 A(1)R signaling pathways in both tissues, showing an A(1)R down-regulation in fetal brain, and desensitization in maternal brain.
León
David
D
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Albasanz
José Luis
JL
Castillo
Carlos Alberto
CA
Martín
Mairena
M
D058916:Adenosine A1 Receptor Antagonists; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D010949:Plasma / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000493:pharmacokinetics
D058916:Adenosine A1 Receptor Antagonists; D005971:Glutamates; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases