The Activation of β2-Adrenergic Receptors in Naïve Rats Causes a Reduction of Blood Glutamate Levels: Relevance to Stress and Neuroprotection
- 130 Downloads
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.
Keywordsβ2-Adrenergic receptors Glutamate Recovery Traumatic brain injury
The authors thank Dorit Reymond for her superb technical assistance. This work was supported in part by grants to VIT from the Nella and Leon Benoziyo Center for Neurological Diseases; Braintact Ltd., the Irwin Green Fund for Studying the Development of the Brain, the Carl and Micaela Einhorn-Dominic Institute for Brain Research. VIT is the incumbent of the Louis and Florence Katz-Cohen Chair of Neuropharmacology.
Conflict of Interest
V.I.T received a grant from Braintact Ltd., as well as consultancy fees.
- 13.Teichberg VI, Cohen-Kashi-Malina K, Cooper I, Zlotnik A (2009) Homeostasis of glutamate in brain fluids: an accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies. Neuroscience 158:301–308PubMedCrossRefGoogle Scholar
- 20.Fiordaliso F, De Angelis N, Bai A, Cuccovillo I, Salio M, Serra DM, Bianchi R, Razzetti R, Latini R, Masson S (2007) Effect of beta-adrenergic and renin-angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats. Life Sci 81:951–959PubMedCrossRefGoogle Scholar
- 24.Zlotnik A, Gurevich B, Cherniavsky E, Tkachov S, Matuzani-Ruban A, Leon A, Shapira Y, Teichberg VI (2007) The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury. Neurochem Res 33:1044–1050PubMedCrossRefGoogle Scholar
- 26.Zlotnik A, Gruenbaum SE, Artru AA, Rozet I, Dubilet M, Tkachov S, Brotfain E, Klin Y, Shapira Y, Teichberg VI (2009) The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate. J Neurosurg Anesthesiol 21:235–241PubMedCrossRefGoogle Scholar
- 32.Zlotnik A, Gurevich B, Cherniavsky E, Tkachov S, Matuzani-Ruban A, Leon A, Shapira Y, Teichberg VI (2008) The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury. Neurochem Res 33:1044–1050PubMedCrossRefGoogle Scholar
- 35.Morris GF, Juul N, Marshall SB, Benedict B, Marshall LF (1998) Neurological deterioration as a potential alternative endpoint in human clinical trials of experimental pharmacological agents for treatment of severe traumatic brain injuries. Executive committee of the international selfotel trial. Neurosurgery 43:1372–1374; discussionGoogle Scholar