Rat striatum contains pure population of ET B receptors

Abstract

In most organs of the body, endothelin acts on endothelin ET A and ET B receptors that co-exist (albeit often on different cell types). Although virtually pure endothelin ET A receptors have been identified in some tissues (e.g., lung), no essentially pure endothelin ET B receptor tissue has been reported to date. [ 125I]Endothelin-1 bound to striatal membrane preparations with a K d of 19.4 ± 0.2 pM and B max of 496 ± 8 fmol/mg protein. Endothelin-1 displaced [ 125I]endothelin-1 receptor binding with an IC 50 of 23 pM. The endothelin ET B-selective antagonist BQ788 ( N-cis-2,6-dimethylpiperidinocarbonyl- l-γ-methyl-leucyl- d-l-methoxycarbonyltryptophanyl- d-norleucine) and agonist sarafotoxin 6C displaced [ 125I]endothelin-1 monophasically with IC 50 values of 25 nM and 110 pM, respectively, whereas that of the endothelin ET A-selective antagonist BQ123 (cyclo( d-Trp- d-Asp-Pro- d-Val-Leu)) was 24 μM, values agreeing with cloned human endothelin ET B but not ET A receptors. Receptor autoradiography confirmed that rat striatum (but not white matter) contains essentially exclusively endothelin ET B receptors.