Angiotensin II depresses glutamate depolarizations and excitatory postsynaptic potentials in locus coeruleus through angiotensin II subtype 2 receptors

H. Xiong, K. C. Marshall

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41 Citations (Scopus)

Abstract

A previously reported depression of glutamate responses by angiotensin II was investigated to define the nature of this neuromodulatory effect. Studies were carried out in an in vitro brain slice preparation containing the locus coeruleus, using intracellular recordings, and iontophoretic, micropressure and bath perfusion methods for application of drugs. The angiotensin action was found to be blocked by a non-peptide antagonist specific for the angiotensin type 2 receptor, and not by an antagonist selective for the type 1 receptor. Excitatory postsynaptic potentials mediated primarily by excitatory amino acids were also depressed by angiotensin II. The angiotensin II depressions of glutamate were shown to be strong and highly specific. The low effectiveness of bath-applied compared with iontophoretically or micropressure-applied angiotensin II was found to be at least partly explained by a rapid degradation by peptidases. Ammonium ions and hydrogen ions were also able to depress glutamate responses, but these effects were not specific for locus coeruleus neurons and were mediated independently of the angiotensin actions. Strong depression by angiotensin II of excitatory postsynaptic potentials as well as exogenously applied glutamate strengthens the strong possibility of a physiological role for this neuromodulatory mechanism. The identification of the type 2 angiotensin receptor subtype as the mediator of this effect indicates a novel functional role for this receptor, since previously recognized functions of angiotensin II in the brain, such as vascular and body fluid regulation, have been associated with the type 1 receptor.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalNeuroscience
Volume62
Issue number1
DOIs
StatePublished - Sep 1994

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Locus Coeruleus
Excitatory Postsynaptic Potentials
Angiotensin II
Glutamic Acid
Angiotensins
Baths
Angiotensin II Type 2 Receptor Blockers
Angiotensin Type 2 Receptor
Excitatory Amino Acids
Brain
Body Fluids
Ammonium Compounds
Blood Vessels
Protons
Peptide Hydrolases
Perfusion
Ions
Neurons
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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abstract = "A previously reported depression of glutamate responses by angiotensin II was investigated to define the nature of this neuromodulatory effect. Studies were carried out in an in vitro brain slice preparation containing the locus coeruleus, using intracellular recordings, and iontophoretic, micropressure and bath perfusion methods for application of drugs. The angiotensin action was found to be blocked by a non-peptide antagonist specific for the angiotensin type 2 receptor, and not by an antagonist selective for the type 1 receptor. Excitatory postsynaptic potentials mediated primarily by excitatory amino acids were also depressed by angiotensin II. The angiotensin II depressions of glutamate were shown to be strong and highly specific. The low effectiveness of bath-applied compared with iontophoretically or micropressure-applied angiotensin II was found to be at least partly explained by a rapid degradation by peptidases. Ammonium ions and hydrogen ions were also able to depress glutamate responses, but these effects were not specific for locus coeruleus neurons and were mediated independently of the angiotensin actions. Strong depression by angiotensin II of excitatory postsynaptic potentials as well as exogenously applied glutamate strengthens the strong possibility of a physiological role for this neuromodulatory mechanism. The identification of the type 2 angiotensin receptor subtype as the mediator of this effect indicates a novel functional role for this receptor, since previously recognized functions of angiotensin II in the brain, such as vascular and body fluid regulation, have been associated with the type 1 receptor.",
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