RAT STRIATUM CONTAINS PURE POPULATION OF ET(B) RECEPTORS

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). Al though virtually pure endothelin ET(A) receptors have been identified in some tissues (e.g., lung), no essentially pure endothelin ET(B) rec eptor tissue has been reported to date. [I-125]Endothelin-1 bound to s triatal membrane preparations with a K-d of 19.4 +/- 0.2 pM and B-max of 496 +/- 8 fmol/mg protein. Endothelin-1 displaced [I-125]endothelin -1 receptor binding with an IC50 of 23 pM. The endothelin ET(B)-select ive antagonist BQ788 ucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine ) and agonist sarafotoxin 6C displaced [I-125]endothelin-1 monophasica lly with IC50 values of 25 nM and 110 pM, respectively, whereas that o f the endothelin ET(A)-selective antagonist BQ123 (cyclo(D-Trp-D-Asp-P ro-D-Val-Leu)) was 24 mu M, values agreeing with cloned human endothel in ET(B) but not ET(A) receptors. Receptor autoradiography confirmed t hat rat striatum (but not white matter) contains essentially exclusive ly endothelin ET(B) receptors.