Pharmacological Differences Between Rat and Human Endothelin B Receptors

Cloned rat and human endothelin-B receptors (ETBR) were utilized to determine if there are significant pharmacological differences between highly homologous ETBR from different species. Recombinant rat and human ETBR were expressed in CHO-K1 cells, and radioligand binding studies were carried out wi...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1995-04, Vol.209 (2), p.506-512
Main Authors: Reynolds, E.E., Hwang, O., Flynn, M.A., Welch, K.M., Cody, W.L., Steinbaugh, B., He, J.X., Chung, F.Z., Doherty, A.M.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Binding, Competitive
Endothelin Receptor Antagonists
Endothelins - metabolism
Humans
Molecular Sequence Data
Radioligand Assay
Rats
Receptor, Endothelin B
Receptors, Endothelin - agonists
Receptors, Endothelin - metabolism
Recombinant Proteins
Species Specificity
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Summary:Cloned rat and human endothelin-B receptors (ETBR) were utilized to determine if there are significant pharmacological differences between highly homologous ETBR from different species. Recombinant rat and human ETBR were expressed in CHO-K1 cells, and radioligand binding studies were carried out with [125I]-ET-3 to determine the affinities of various ET receptor agonists and antagonists for rat and human ETBR. These receptors had similar affinities for a number of ETBR agonists (ET-1, ET-3, S6C, BQ 3020) and antagonists (Ro 47-0203, PD 142893). However, several peptide (PD 147452, PD 151583, BQ 788) and non-peptide (PD 156707, SE 209670) antagonists had different affinities for rat and human ETBR, with differences in Ki values between species ranging from 4.1- to 53.4-fold. The ETBR-selective agonist IRL 1620 also had a 5.7-fold higher affinity for rat ETBR than human ETBR. Thus despite their high degree of homology, rat and human ETBR show significant pharmacological differences with respect to both antagonist and agonist binding.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1995.1530