Chronic intake of caffeine during gestation down regulates metabotropic glutamate receptors in maternal and fetal rat heart

Amino Acids. 2006 May;30(3):257-66. doi: 10.1007/s00726-005-0293-7. Epub 2006 Apr 13.


Caffeine is the most widely consumed substance in the world which antagonizes adenosine effects. Adenosine acting through A(1) receptors inhibits glutamate release which binds to metabotropic glutamate receptors (mGluRs). Recently, we have shown that maternal caffeine intake during gestation causes down-regulation of A(1) and metabotropic glutamate receptors in the brain of both rat mothers and fetuses. In the present work we provide evidence that caffeine also affects receptors in hearts, causing a decrease in mGluRs from both maternal and fetal hearts. A decrease in G(q/11) and PLC beta(1) proteins level was also observed in both tissues. However, phospholipase C activity was only affected in fetal heart, being significantly decreased. These results suggest an in vivo cross-talk mechanism between adenosine and glutamate receptors in peripheral tissues. Therefore, special attention should be paid to caffeine ingestion during gestation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / embryology
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Down-Regulation / drug effects*
  • Female
  • Fetal Heart / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Gene Expression Regulation, Developmental / drug effects*
  • Isoenzymes / metabolism
  • Maternal-Fetal Exchange / drug effects
  • Phospholipase C beta
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A1 / metabolism
  • Receptors, Metabotropic Glutamate / biosynthesis*
  • Type C Phospholipases / metabolism


  • Central Nervous System Stimulants
  • Isoenzymes
  • Receptor, Adenosine A1
  • Receptors, Metabotropic Glutamate
  • Caffeine
  • Type C Phospholipases
  • Phospholipase C beta
  • Plcb1 protein, rat
  • GTP-Binding Protein alpha Subunits, Gq-G11