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

The phenylalkylamine emopamil prevents brain damage due to experimental cerebral ischemia. Stereoselective, high affinity, binding sites for (-)-[ 3 H]emopamil in guinea pig brain cortex and liver membranes have been proposed to mediate its antiischemic effect. Using [N-methyl- 3 H]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