ANGIOTENSIN-II DEPRESSES GLUTAMATE DEPOLARIZATIONS AND EXCITATORY POSTSYNAPTIC POTENTIALS IN LOCUS-COERULEUS THROUGH ANGIOTENSIN-II SUBTYPE2 RECEPTORS

A previously reported depression of glutamate responses by angiotensin II was investigated to define the nature of this neuromodulatory effe ct. Studies were carried out in an in vitro brain slice preparation co ntaining the locus coeruleus, using intracellular recordings, and iont ophoretic, micropressure and bath perfusion methods for application of drugs. The angiotensin action was found to be blocked by a non-peptid e antagonist specific for the angiotensin type 2 receptor, and not by an antagonist selective for the type I receptor. Excitatory postsynapt ic potentials mediated primarily by excitatory amino acids were also d epressed by angiotensin II. The angiotensin II depressions of glutamat e were shown to be strong and highly specific. The low effectiveness o f bath-applied compared with iontophoretically or micropressure-applie d angiotensin II was found to be at least partly explained by a rapid degradation by peptidases. Ammonium ions and hydrogen ions were also a ble to depress glutamate responses, but these effects were not specifi c for locus coeruleus neurons and were mediated independently of the a ngiotensin actions. Strong depression by angiotensin II of excitatory postsynaptic potentials as well as exogenously applied glutamate stren gthens the strong possibility of a physiological role for this neuromo dulatory mechanism. The identification of the type 2 angiotensin recep tor subtype as the mediator of this effect indicates a novel functiona l role for this receptor, since previously recognized functions of ang iotensin II in the brain, such as vascular and body fluid regulation, have been associated with the type 1 receptor.