Angiotensin II depresses glutamate depolarizations and excitatory postsynaptic potentials in locus coeruleus through angiotensin II subtype 2 receptors.
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 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.
Xiong
H
H
Department of Physiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Marshall
K C
KC
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology*; D006859:Hydrogen / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000644:Quaternary Ammonium Compounds; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D018698:Glutamic Acid; D006859:Hydrogen