Effect of chronic gestational treatment with caffeine or theophylline on Group I metabotropic glutamate receptors in maternal and fetal brain

Abstract

Pregnant rats were treated throughout the gestational period with either caffeine or theophylline, and its effect on the metabotropic glutamate receptor (mGluRs) signal transduction pathway was studied in both maternal and fetal brain. In maternal brain, radioligand binding assays showed that chronic treatment with methylxanthines caused a significant decrease in the total number of mGluRs. This decrease was accompanied by an increase in receptor affinity. Immunodetection showed that mGluR 1a and phospholipase C b 1 (PLCb 1 ) were significantly decreased in response to chronic methylxanthine treatment, whereas aG q/11 was not affected. A loss was also detected of PLC stimulation mediated by (S)-3,5-dihydroxyphenylglycine (DHPG), a selective Group I mGluR agonist, suggesting desensitization of the mGluR/PLC pathway. In fetal brain, a loss in total mGluRs was observed in fetuses from mothers treated with caffeine or theophylline, without variation in receptor affinity. A decrease in mGluR 1a , aG q/11 and PLCb 1 levels was also observed in response to treatment. However, changes detected in this immature tissue were not associated with variations in PLC activity. These results suggest that chronic caffeine or theophylline treatment down-regulates several mGluR/PLC transduction pathway components in both maternal and fetal brain, causing a loss of receptor responsiveness only in maternal brain.

Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats

“…Thus, exposure to caffeine during development can have long-term effects on adenosine receptor expression. Further, the levels of mGluRs are decreased in the fetal brain following caffeine and theophylline treatment [28]. Enduring changes in adenosinergic and glutamatergic receptor expression following perinatal caffeine exposure may contribute to changes in learning and memory.…”

Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth

“…Leon et al (28) reported that chronic caffeine or theophylline treatment downregulated group I metabotropic glutamate receptors, one of the G protein-coupled membrane-bound receptor superfamily, in both maternal and fetal brains in a rat animal model. In the present study, we found that the maternal caffeine effects on embryonic CV function occurred via adenosine A 2A receptor blockade.…”

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

“…Equal loading and even transfer of protein gels was confirmed visually by staining the blot with the reversible dye Ponceau S prior to incubation with antibody. Western blotting was performed as described elsewhere (León et al, 2005a). Immunodetection was carried out by incubating the nitrocellulose membranes with specific polyclonal antibodies (anti‐mGlu 1 receptor, anti‐mGlu 5 receptor, and anti‐αG q/11 ) diluted 1:1,000 and isoenzyme‐specific monoclonal antibody (anti‐PLCβ 1 ) diluted 1:400. β‐Actin antibody (1:5,000) was used as a gel loading control.…”

“…Although the cross‐interaction between metabotropic glutamate and adenosine receptors has been described from several in vitro approaches, including cerebrocortical nerve terminals (Vazquez et al, 1995), hippocampal slices (de Mendonca and Ribeiro, 1997), and cultured cells (Ogata et al, 1996; Cartmell et al, 1998; Toms and Roberts, 1999), little is known about cross‐talk between these receptors after chronic in vivo activation of one of these signal transduction pathways. Previously, we have described that oral administration of caffeine or theophylline, antagonists of adenosine A 1 receptors, to pregnant rats down‐regulates several mGlu/PLC transduction pathway components in both maternal and fetal brain, causing a loss of receptor responsiveness only in maternal brain (León et al, 2005a). On the other hand, R‐phenylisopropyladenosine (R‐PIA) chronically administered to male rats during 6 days caused a significant increase in the mGlu/PLC pathway from the brain (Albasanz et al, 2002).…”