Open AccessA Correlation Between Dexmedetomidine-Induced Biphasic Increases in Free Cytosolic Calcium Concentration and Energy Metabolism in Astrocytes
Author(s) -
Ye Chen,
Zhiqiang Zhao,
William E. Code,
Leif Hertz
Publication year - 2000
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1097/00000539-200008000-00022
Subject(s) - idazoxan , dexmedetomidine , yohimbine , imidazoline receptor , medicine , endocrinology , metabolism , agonist , astrocyte , cytosol , calcium , biology , pharmacology , biochemistry , receptor , antagonist , central nervous system , prazosin , sedation , enzyme
The alpha(2)-adrenergic agonist, dexmedetomidine, increases free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, but not in neurons. The present study was performed to characterize the origin of the increased Ca(2+) in mouse astrocytes cultured from the cerebral cortex, the dose dependence of the effect, and its functional consequences. The increase in [Ca(2+)](i) was independent of extracellular Ca(2+), but was inhibited by dantrolene, showing that it is derived from intracellular stores; two peaks in [Ca(2+)](i) were demonstrated-one around 100 nM dexmedetomidine and the other in the low micromolar range. A similar dose dependence was found for pyruvate dehydrogenation, the initial metabolic reaction of oxidative degradation of pyruvate, suggesting that the these events are interrelated. The alpha(2)-adrenergic antagonist, yohimbine, abolished the metabolic stimulation at both peaks. However, whereas the increase in [Ca(2+)] (i) at 100 nM is abolished by yohimbine, increase in the micromolar range was partly inhibited by yohimbine and partly by idazoxan, an inhibitor at the imidazoline-preferring site. The stimulation of energy metabolism in cerebrocortical astrocytes may explain the repeated finding that dexmedetomidine does not decrease oxidative metabolism in the brain in vivo. The functional importance of the additional imidazoline receptor-mediated increase in [Ca(2+)](i) at large dexmedetomidine concentrations is unknown.