The Activation of β2-Adrenergic Receptors in Naïve Rats Causes a Reduction of Blood Glutamate Levels: Relevance to Stress and Neuroprotection

Abstract

This study examines the effects of the activation of β1 and β2-adrenergic receptors on glutamate homeostasis in the blood of naïve rats. Forty five male Sprague-Dawley rats were randomly assigned into one of seven treatment groups that were treated with various β-adrenergic receptor agonist and antagonist drugs. Blood glutamate levels were determined at t = 0, 30, 60, 90, and 120 min. The activation of β1 and β2-adrenergic receptors via isoproterenol hydrochloride administration produced a marked sustained decrease in blood glutamate levels by 60 min after treatment (ANOVA, t = 60, 90 min: P < 0.05, t = 120 min: P < 0.01). Pretreatment with propranolol hydrochloride (a non-selective β-adrenergic receptor blocker) or butaxamine hydrochloride (a selective β2-adrenergic receptor blocker) occluded the isoproterenol-mediated decrease in blood glutamate levels. Propranolol alone had no effect on blood glutamate levels. Selective β1-adrenergic receptor blockade with metoprolol resulted in decreased blood glutamate levels (ANOVA, t = 90 min: P < 0.05, t = 120 min: P < 0.01). Butaxamine hydrochloride alone resulted in a delayed-onset increase in glutamate levels (ANOVA, t = 120 min: P < 0.05). The results suggest that the activation of β2 receptors plays an important role in the homeostasis of glutamate in rat blood.

The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

“…Therefore, to reduce glutamate neurotoxicity, it was suggested that we regulate the levels of glutamate in the cerebrospinal fluid (CSF) and ECF by use of familiar mechanisms of glutamate transport from the brain to the blood. In our laboratory, we previously examined various mechanisms to lower glutamate levels including by activation of β 2 -adrenergic receptors and different kinds of hormones [21,[24][25][26].…”

“…Previous studies done by our group and others have shown that pharmacologically reducing blood glutamate levels with glutamate scavengers (such as oxaloacetate and pyruvate) limit glutamate neurotoxicity and provide better neurologic outcomes after various brain insults, particularly traumatic brain injury [14,[19][20][21][44][45][46][47][48][49][50][51][52][53]. Unfortunately, although these treatments have been shown to be effective in animal models of stroke, traumatic brain injury, and subarachnoid hemorrhage, their use in humans is limited by Food and Drug administration restrictions.…”

Glutamate as a neurotransmitter in the healthy brain

“…This is important for a number of reasons. One of them is the fact that serum glutamate is typically in the range 50–200 μm (Zlotnik et al 2011a, b, c) which is orders of magnitude higher than the concentrations that are toxic to neurons (Danbolt 2001). …”

Effect of estrogens on blood glutamate levels in relation to neurological outcome after TBI in male rats

“…This short-lived phenomenon may be related to activation of the sympathetic nervous system [27], possibly augmenting efflux of excess brain glutamate, contributing to the trend of spontaneous neurological improvement observed in all TBI groups 24 h post injury [16]. The significant increase of blood glutamate concentration at 60 min, ''overshooting'' baseline values, may reflect several processes, including overwhelming of the glutamate metabolism mechanisms and increased distribution from brain ECF and peripheral tissue into the blood [15,16,28].…”