Effect of chronic gestational treatment with the adenosine A1 receptor agonist R-phenylisopropyladenosine on metabotropic glutamate receptors/phospholipase C pathway in maternal and fetal brain
✍ Scribed by David A. León; José L. Albasanz; Carlos A. Castillo; Inmaculada Iglesias; Mairena Martín
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 297 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
Pregnant Wistar rats were orally treated with the adenosine receptor agonist R‐phenylisopropyladenosine (R‐PIA) throughout the gestational period, and the status of the metabotropic glutamate (mGlu) receptor/phospholipase C transduction pathway from maternal and fetal brain was analyzed. In mothers' brains, radioligand binding assays revealed a significant decrease in the Bmax value, without any significant alteration in Kd value. Similar results were observed in the steady‐state level of mGlu~1~ and mGlu~5~ receptors assayed by Western blot, suggesting that both receptor subtypes were modulated by chronic R‐PIA treatment. mRNA coding mGlu~1~ or mGlu~5~ receptors was not altered, suggesting a posttranscriptional modulation as a possible mechanism of the loss of mGlu~1~ and mGlu~5~ receptors at the membrane surface. Moreover, phospholipase C stimulated by (R,S)‐3,5‐dihydroxyphenylglycine (DHPG), a selective agonist of group I mGlu receptors, was also significantly decreased after R‐PIA treatment, suggesting a heterologous desensitization of group I mGlu/PLC pathway in maternal brain. Western blot and RT‐PCR assays showed that neither αG~q/11~ nor PLCβ~1~ was affected by R‐PIA treatment. In fetal brain, no significant differences in mGlu receptors/PLC transduction pathway were observed after R‐PIA treatment. These results suggest that chronic R‐PIA intake during pregnancy modulates group I mGlu receptor signalling pathway in maternal brain, promoting a down‐regulation of mGlu~1~ and mGlu~5~ receptors and a heterologous desensitization of the mGlu/PLC system. © 2008 Wiley‐Liss, Inc.