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.

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 alphaG(q/11) nor PLCbeta(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.