Rat striatum contains pure population of ETB receptors.
In most organs of the body, endothelin acts on endothelin ETA and ETB receptors that co-exist (albeit often on different cell types). Although virtually pure endothelin ETA receptors have been identified in some tissues (e.g., lung), no essentially pure endothelin ETB receptor tissue has been reported to date. [125I]Endothelin-1 bound to striatal membrane preparations with a Kd of 19.4 +/- 0.2 pM and Bmax of 496 +/- 8 fmol/mg protein. Endothelin-1 displaced [125I]endothelin-1 receptor binding with an IC50 of 23 pM. The endothelin ETB-selective antagonist BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma -methyl-leucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine) and agonist sarafotoxin 6C displaced [125I]endothelin-1 monophasically with IC50 values of 25 nM and 110 pM, respectively, whereas that of the endothelin ETA-selective antagonist BQ123 (cyclo(D-Trp-D-Asp-Pro-D-Val-Leu)) was 24 microM, values agreeing with cloned human endothelin ETB but not ETA receptors. Receptor autoradiography confirmed that rat striatum (but not white matter) contains essentially exclusively endothelin ETB receptors.
Tayag
E C
EC
Department of Neurosurgery, Medical College of Pennsylvania, Philadelphia 19102-1192, USA.
Jeng
A Y
AY
Savage
P
P
Lehmann
J C
JC
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D016466:CHO Cells / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000032:analysis / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000032:analysis / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)