1. The linear tetrapeptide radioligand, [125I]-PD151242 was used to characterize ETA receptors in human kidney which is an ETB-rich tissue. Saturation binding assays with [125I]-PD151242 revealed a single population of high affinity endothelin receptors: KD = 0.75 +/- 0.07 nM and Bmax = 48.4 +/- 1.6 fmol mg-1 protein (n = 3 individuals +/- s.e.mean). Hill slopes were close to unity and a one site fit was preferred to a two site model. 2. ETA-receptor-selective ligands competed for [125I]-PD151242 binding with sub-nanomolar affinity: BQ123 KD = 0.43 +/- 0.10 nM, Bmax = 46.6 +/- 7.9 fmol mg-1 protein; FR139317, KD = 0.37 +/- 0.06 nM, Bmax = 39.5 +/- 6.5 fmol mg-1 protein (n = 3 individuals +/- s.e.mean). In each case, monophasic inhibition curves were obtained and a one site fit was preferred to a two site model. The ETB-selective agonist, BQ3020 at the highest concentration tested (10 microM) inhibited binding by only 50%. The non-selective RO462005 competed for the binding of [125I]-PD151242: KD = 1.31 +/- 1.38 microM, Bmax = 33.0 +/- 9.7 fmol mg-1 protein. Endothelin-2 and sarafotoxin S6B inhibited [125I]-PD151242 binding to renal tissue whereas ET-3 and sarafotoxin S6C were less effective. Non-endothelin and non-sarafotoxin peptides did not compete. 3. No degradation of [125I]-PD151242 was detected following incubation of the ligand with renal tissue under the conditions of the binding assay.(ABSTRACT TRUNCATED AT 250 WORDS
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