Effect of glutamate intake during gestation on adenosine A₁ receptor/adenylyl cyclase pathway in both maternal and fetal rat brain

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 Bmax value, although the Kd value was significantly decreased. However in fetus brain, a significant decrease in Bmax was observed, without an alteration of Kd 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.

Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors

“…However, in this case, we observed a significant decrease of mGlu 1 and mGlu 5 receptors and a corresponding desensitization of mGlu receptor/PLC signalling pathway [35] which suggest that crosstalk processes may be influenced by different parameters such as gender or routes of administration. In reciprocal experiments, continuous L-glutamate intake throughout gestation also decreased A 1 receptor/AC signalling pathway in the maternal brain [36]. Finally, we have observed not only changes in group I-mGlu receptors functionality upon prolonged exposure to A 1 receptor agonist but also we showed a loss of group I-mGlu receptors responsiveness following chronic caffeine exposure which suggests that the blockade of adenosine receptors might also alter mGlu receptor functionality [37].…”

Re‐evaluation of glutamic acid (E 620), sodium glutamate (E 621), potassium glutamate (E 622), calcium glutamate (E 623), ammonium glutamate (E 624) and magnesium glutamate (E 625) as food additives

“…Glutamic acid hydrochloride was administered at 2 and 4 g/kg bw as a 20% (w/v) solution and sucrose (in 80% w/v) was given at dosages equimolar to 4, 8 or 10 g MSG/kg bw. Oedema and pyknotic nuclei were seen in sodium chloride-treated animals of 5 days of age; no lesions were seen in animals older than 6 days at the time of treatment, nor in mice given sucrose' (Lemkey-Johnston et al, 1975as referred to by JECFA, 1988.…”

“…In another study, pregnant Wistar rats (not further specified) were given L-glutamate at a concentration of 0 or 1,000 mg/L (equal to 0 or 110 mg/kg bw per day) in the drinking water from gestational day 2 and during the whole gestational period (Le on et al, 2008). Brains of both mothers and their offspring were then isolated.…”

Maternal monosodium glutamate intake influences the learning ability of the offspring of sprague dawley rats

“…Leon et al suggested that glutamate administered to pregnant rats modulates adenosine A1 receptor signaling pathways in both maternal and fetal brain, showing an adenosine A1 receptor down-regulation in fetal brain, and desensitization in maternal brain. 32 MSG in high doses caused neuronal necrosis in hypothalamic arcuate nuclei in neonatal rats. 33 MSG (4 mg/g.…”