PMID: 8587419Jan 1, 1995Paper

Characterization of peptide and nonpeptide antagonists in human kidney

Journal of Cardiovascular Pharmacology
R E KucA P Davenport

Abstract

The human kidney contains about 70% endothelin ETB receptors, with the remaining ETA subtype mainly localized to the vasculature. Our aim was to characterize new ligands using native human receptors present in this tissue. In competition binding assays, sections of kidney (n > or = 3 individuals, +/- SEM) were incubated with 100 pM [125I]ET-1 and increasing concentrations of unlabeled ligands. The nonpeptide antagonists inhibited [125I]ET-1 binding monophasically (bosentan, Kd 360 +/- 50 nM, Bmax 39.5 +/- 9.4 fmol/mg protein; SB209670, Kd 80.0 +/- 12.5 nM, Bmax 51.8 +/- 20.4 fmol/mg protein). The ETB agonist sarafotoxin S6c competed biphasically with 1,400-fold selectivity for the ETB subtype (Kd ETA 2.2 +/- 0.2 microM, Bmax 22.6 +/- 4.9 fmol/mg protein; Kd ETB 1.5 +/- 0.2 nM, Bmax 46.3 +/- 9.0 fmol/mg protein). In contrast, BQ788 (an ETB antagonist in animals) competed monophasically (Kd 125.9 +/- 10.3 nM) and is not selective for the human renal ETB receptor. The ETA-selective antagonist S97-139 competed biphasically, with high affinity and 1,100-fold selectivity for the ETA site (Kd ETA 4.4 +/- 4.0 nM), but low affinity for ETB receptors (Kd ETB 5.1 +/- 0.4 microM). Autoradiography showed that ETA-selective compounds inhibit...Continue Reading

Citations

Mar 10, 2016·Pharmacological Reviews·Anthony P DavenportJanet J Maguire
May 13, 2015·Seminars in Nephrology·Janet J Maguire, Anthony P Davenport
Feb 6, 1999·European Journal of Radiology·S K MorcosJ O Karlsson

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