Opposing effects on blood pressure following the activation of metabotropic and ionotropic glutamate receptors in raphe obscurus in the anaesthetized rat

Naunyn Schmiedebergs Arch Pharmacol. 1996 Feb;353(3):302-5. doi: 10.1007/BF00168632.

Abstract

The microinjection of L-glutamate (1-6 nmol/rat) and N-methyl-D-aspartate (NMDA 1-10 nmol/rat), ionotropic glutamate receptor (iGluR) agonists, into the nucleus raphe obscurus caused a concentration -dependent increase of arterial blood pressure. In contrast, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD, 14-42 nmol/rat), a metabotropic glutamate receptor (mGluRs) agonist, caused a concentration-dependent decrease in blood pressure. Pretreatment with D,L-2-amino-phosphono valeric acid (2-APV, 5 nmol/rat) a selective NMDA iGluR antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b] cyclohepten-5,10-imine hydrogen maleate (MK801, 0.9 nmol/rat), a noncompetitive NMDA iGluR antagonist, blocked both the glutamate and NMDA pressor responses, while pretreatment with (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 0.05 nmol/rat), a mGluR1 antagonist, increased the glutamate-induced pressor effects and blocked the fall in blood pressure induced by t-ACPD. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.4 nmol/rat) a non-NMDA iGluR antagonist, did not affected the glutamate-induced hypertension. These observations indicate opposing roles for ionotropic and metabotropic receptors in the glutamate-induced blood pressure changes elicited from the nucleus raphe obscurus. Moreover, we suggest that the glutamate-induced hypertension may be due to the activation of NMDA ionotropic receptor subtypes and the metabotropic receptors may influence this activation through a reduction of excitability at level of synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / administration & dosage
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Analysis of Variance
  • Animals
  • Benzoates / administration & dosage
  • Benzoates / pharmacology
  • Blood Pressure / drug effects*
  • Cycloleucine / administration & dosage
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glutamic Acid / administration & dosage
  • Glutamic Acid / toxicity
  • Glycine / administration & dosage
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hypertension / chemically induced
  • Hypertension / etiology
  • Male
  • Microinjections
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / pharmacology
  • Neurotoxins / administration & dosage
  • Neurotoxins / pharmacology
  • Raphe Nuclei / drug effects*
  • Raphe Nuclei / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / drug effects*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship
  • Valine / administration & dosage
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Benzoates
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neurotoxins
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • alpha-methyl-4-carboxyphenylglycine
  • Glutamic Acid
  • N-Methylaspartate
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Valine
  • Glycine