Metabotropic glutamate receptor/phospholipase C system in female rat heart

Brain Res. 2007 Jun 11:1153:1-11. doi: 10.1016/j.brainres.2007.01.010. Epub 2007 Jan 9.

Abstract

Glutamate is the main excitatory neurotransmitter in the central nervous system. This amino acid mediates learning and memory processes acting through ionotropic and metabotropic receptor binding. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors that stimulate phospholipase C (PLC) or inhibit adenylyl cyclase (AC). MGluRs have been widely described in CNS. However, little is known about these receptors in peripheral system. The present work describes the mGluR/PLC pathway in membranes from pregnant and non-pregnant rat heart by radioligand binding, Western-blot assays and PLC activity determination. Furthermore, mRNA coding mGluR1, mGluR5, alphaGq/11 and PLCbeta1 was identified by RT-PCR. Binding assays indicated total mGlu receptor numbers of 4.7+/-0.2 pmol/mg protein and 4.2+/-1.0 pmol/mg protein in non-pregnant and pregnant rats respectively, and their corresponding KD values were 545.3+/-85.6 nM and 1062.8+/-393.6 nM. Western blots revealed bands corresponding to mGluR1 and mGluR5 receptors, confirming that these receptors are expressed in heart. The beta1 isoform of PLC, which mediates group I mGluRs (mGluR I) response, was also expressed in rat heart. Moreover, PLC activity was modulated by calcium in a dose-dependent manner. Finally, specific agonists for mGluRs increased the PLC activity and the increase was prevented by specific mGluR antagonists. These results demonstrate the presence of group I mGlu receptors and their functional coupling to the PLC stimulation in female rat heart, suggesting a possible role of mGluR/PLC pathway in this tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Blotting, Western
  • Calcium / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacokinetics
  • Female
  • Gene Expression
  • Glutamic Acid / pharmacokinetics
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Pregnancy
  • Quisqualic Acid / pharmacokinetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Type C Phospholipases / metabolism*

Substances

  • Excitatory Amino Acid Agonists
  • RNA, Messenger
  • Receptors, Metabotropic Glutamate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Glutamic Acid
  • Quisqualic Acid
  • Type C Phospholipases
  • Calcium