title: Regulation of blood L-glutamate levels by stress as a possible brain defense mechanism.
abstract: Isoflurane-anesthetized rats submitted to a closed head injury (CHI) display a significant decrease of their blood glutamate levels. Having demonstrated that a decrease of blood L-glutamate (glutamate) causes an increase of the driving force for a spontaneous brain-to-blood glutamate efflux, and consequently affords brain neuroprotection, we investigated here the possible mechanisms which can affect blood glutamate levels. Reasoning that the spontaneous decrease of blood glutamate levels post CHI could be part of a stress response, we observed that the stress involved in tail artery catheterization under isoflurane anesthesia does not affect blood glutamate levels. Investigating in naïve rats the stress effectors, we found that corticotropin-releasing factor (CRF) significantly decreased blood glutamate levels. Pretreatment with antalarmine (a selective type-1 CRF receptor antagonist) occludes the CRF-mediated decrease in blood glutamate levels. In contrast, the adrenocorticotrophic hormone (ACTH) did not affect blood glutamate levels. Investigating the effectors of the sympathetic/adrenomedullary system, we observed that in naïve rats, adrenaline but not noradrenaline decreased blood glutamate levels. Confirming the role of adrenaline, propranolol pretreatment (a non-selective beta-antagonist) prevented the spontaneous decrease of blood glutamate observed post CHI. On the strength of these results, we further observed that isoproterenol (a beta(1/2)-selective adrenoreceptor agonist) produced a marked sustained decrease in blood glutamate levels. These results suggest that stress induces a decrease of blood glutamate levels partly via the activation of peripheral CRF receptors and the activation of the beta-adrenoreceptors. We propose that this newly identified component of the stress response could be a peripherally mediated defense mechanism of the injured brain against the deleterious effects of excess glutamate.
authors.affiliation: The Division of Anesthesiology, Soraka Medical Center and Ben Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Yael
authors.initials: Y
authors.lastname: Klin
authors.forename: Ruslan
authors.initials: R
authors.lastname: Kotz
authors.forename: Michael
authors.initials: M
authors.lastname: Dubilet
authors.forename: Mathew
authors.initials: M
authors.lastname: Boyko
authors.forename: Sharon
authors.initials: S
authors.lastname: Ohayon
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D018698:Glutamic Acid / Q000097:blood*; D016489:Head Injuries, Closed / Q000097:blood* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D013312:Stress, Physiological; D000099052:CRF Receptor, Type 1
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011743:Pyrimidines; D011758:Pyrroles; D011943:Receptors, Adrenergic, beta; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D018698:Glutamic Acid; D000099052:CRF Receptor, Type 1; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011433:Propranolol; D007545:Isoproterenol; D004837:Epinephrine