Effect of anesthetics on calcium stores and membrane order of brain microsomes.
The effects of anesthetic agents from different chemical classes and a nonanesthetic membrane-disordering agent, 2-[2-methoxyethoxy]ethyl-8-[cis-2-n-octylcyclopropyl]octanoate (A2C), on calcium stores of whole brain microsomes and on order of microsomal membranes were compared. Calcium release was determined by measurement of the extramicrosomal calcium concentration and membrane order by the fluorescence polarization of diphenylhexatriene (membrane core) and trimethylammonium-diphenylhexatriene (membrane "surface"). n-Alkanols (methanol, ethanol, propanol, butanol, pentanol, and hexanol), benzyl alcohol (10-100 mM), and diethyl ether (30-300 mM) released calcium from brain microsomes and decreased the surface and interior membrane order of microsomal membranes. Pentobarbital (0.05-1 mM) did not release calcium from microsomes and did not alter the order of brain microsomal membranes. Halogenated anesthetics (halothane, methoxyflurane, and enflurane), 4-phenyl-1-butanol, and A2C decreased membrane order but failed to release calcium from brain microsomes. Comparison of the effects of these agents on microsomal calcium release and order of microsomal membranes revealed that decreases in membrane order are unrelated to the calcium-mobilizing actions of anesthetic compounds. In addition, molecular size appeared to limit ability of anesthetic compounds to release calcium from microsomes. For n-alkanols, benzyl alcohol, and diethyl ether, the ability to release microsomal calcium was correlated with anesthetic potency. Our results demonstrate, for the first time, direct effects of anesthetic agents on intracellular calcium stores of brain tissue and indicate that these stores may be target sites for anesthetics.
Daniell
L C
LC
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Harris
R A
RA
D000438:Alcohols / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D004986:Ether / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008861:Microsomes / Q000187:drug effects* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D000438:Alcohols; D000777:Anesthetics; D004986:Ether; D002118:Calcium