Biochemical characterization of a 22-kDa high affinity antiischemic drug- binding polypeptide in the endoplasmic reticulum of guinea pig liver: Potential common target for antiischemic drug action

F. F. Moebius, G. G. Burrows, J. Striessnig, H. Glossmann

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31 Scopus citations


The phenylalkylamine emopamil prevents brain damage due to experimental cerebral ischemia. Stereoselective, high affinity, binding sites for (-)- [3H]emopamil in guinea pig brain cortex and liver membranes have been proposed to mediate its antiischemic effect. Using [N-methyl-3H]LU49888 as a photoaffinity probe we now provide evidence that the cation-sensitive emopamil binding site is localized on a 22-kDa polypeptide in guinea pig liver, kidney, lung, and adrenal gland. This 22-kDa polypeptide binds other antiischemic drugs with high affinity and is a nonglycosylated integral membrane protein of the endoplasmic reticulum. It can be solubilized with digitonin without changes in its drug-binding properties. The solubilized binding activity has a sedimentation coefficient of 12.0 ± 0.4 S and an apparent Stokes radius of 6.0 ± 0.1 nm. From these data it is concluded that the 22-kDa polypeptide is associated in a larger oligomeric complex with a molecular mass of at least 84 kDa. [N-methyl-3H]LU49888 also specifically labels a second 27-kDa polypeptide in the endoplasmic reticulum, which can be distinguished from the 22-kDa polypeptide by its pharmacological and hydrodynamic properties. The photolabeled 22-kDa polypeptide was partially purified under denaturing conditions. This will allow the further structural analysis of this putative target for antiischemic drugs.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalMolecular pharmacology
Issue number2
StatePublished - Jan 1 1993


ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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