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.
León
David A
DA
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 L
JL
Castillo
Carlos A
CA
Iglesias
Inmaculada
I
Martín
Mairena
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus; D018811:Maternal Exposure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000187:drug effects*
D058907:Adenosine A1 Receptor Agonists; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C047235:N-(1-methyl-2-phenylethyl)adenosine; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000241:Adenosine