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

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Brennan LK, Froemming GR, Ohlendieck K

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

Biochem Biophys Res Commun. 2000 May 19;271(3):770-6. doi: 10.1006/bbrc.2000.2688.

PubMed ID

10814537 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Halothane	Plasma membrane calcium-transporting ATPase (Protein Group)	Protein group	Humans	Yes	Inhibitor	Details