Type

Journal Article

Authors

K Ohlendieck
G R Froemming
L K Brennan

Subjects

Biochemistry

Topics
sarcoplasmic reticulum animals isoenzymes enzymology chemistry immunology antibodies monoclonal anesthetics binding sites muscle skeletal cross linking reagents halothane rabbits electrophoresis polyacrylamide gel metabolism immunoblotting calcium transporting atpases drug effects protein conformation detergents pharmacology

Effect of halothane on the oligomerization of the sarcoplasmic reticulum Ca(2+)-ATPase. (2000)

Abstract The exact molecular mechanism of inhalational anesthetics remains obscure. Since the enzyme activity of the sarcoplasmic reticulum Ca(2+)-ATPase from skeletal muscle fibres is modified by halothane and because protein-protein interactions play an important role in the regulation of Ca(2+)-regulatory proteins, we investigated the effect of this volatile drug on the oligomerization of the fast-twitch Ca(2+)-ATPase. Using electrophoretic separation following incubation with halothane, increases in relative molecular mass were determined by immunoblotting with a monoclonal antibody to the SERCA1 isoform of the Ca(2+)-ATPase. Distinct drug-induced decreases in electrophoretic mobility indicated oligomerization of the native Ca(2+)-pump by halothane, comparable to crosslinking-mediated formation of homo-tetramers. Determination of the effect of halothane on enzyme activity suggested that halothane-mediated protein aggregation triggers a partial inhibition of Ca(2+)-pump units. Thus, halothane appears to exert its action via specific peptide binding sites and not indirectly by lipid perturbation. These findings support the protein theory of anesthetic action.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

K Ohlendieck, G R Froemming, L K Brennan

Experts in our system

1
Kay Ohlendieck
Maynooth University
Total Publications: 131
 
2
Lorraine Brennan
University College Dublin
Total Publications: 166