Receptor subtype and dose dependence of dexmedetomidine-induced accumulation of [14C]glutamine in astrocytes suggests glial involvement in its hypnotic-sedative and anesthetic-sparing effects.
Dexmedetomidine, a selective alpha(2)-adrenergic agonist, increases accumulation of [14C]glutamine and its labeled metabolites in primary cultures of mouse astrocytes. The concentration dependence is biphasic and identical to that previously described for dexmedetomidine's effect on free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, and both effects are exerted on the alpha(2A) subtype of the alpha(2) receptor, suggesting a Ca(2+)-mediated effect. The concentration corresponding to the most potent effect is similar to that with which dexmedetomidine exerts its anesthetic-sparing activity in vivo, and the second peak corresponds to its hypnotic-sedative effect. It is suggested that both effects may be caused by decreased glutamatergic neurotransmission, secondary to reduced availability of glutamine as a glutamate precursor in glutamatergic neurons.
Huang
R
R
NeoTherapeutics, Irvine, California and Department of Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Hertz
L
L
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C547769:Adra2a protein, mouse; D000777:Anesthetics; D002250:Carbon Radioisotopes; D006993:Hypnotics and Sedatives; D018341:Receptors, Adrenergic, alpha-2; D005973:Glutamine; D018698:Glutamic Acid; D020927:Dexmedetomidine; D002118:Calcium