Characterization of the endothelin receptor selective agonist, BQ3020 and antagonists BQ123, FR139317, BQ788, 50235, Ro462005 and bosentan in the heart

Abstract

concentrations greater than 100 nM in rat and porcine heart. This is in contrast to the data from the ETA-selective antagonists which indicated the presence of ETB sites in these tissues from animal hearts. 4 The peptide antagonist, BQ788, had a low, micromolar affinity (KD= 1.98 + 0.13 gM) using human left ventricle and no significant selectivity for the human ETB-subtype in this tissue.5 The non-peptide ET antagonists, Ro462005 (KD= 50.3 + 9.5 gM) and bosentan (Ro470203; KD= 77.9 + 7.9 nM) competed monophasically for ['251]-ET-I binding sites in human left ventricle. 6 The results show that the ETA antagonists, BQ123 and FR139317, are highly selective for ETA receptors in all cardiac tissues tested, whereas BQ788 has a low affinity and no selectivity in this human tissue. Further we showed that there are species differences in the binding of BQ3020 to the ETB receptors in the hearts derived from human, rat and pig.

Identification of Endothelin Receptor Subtypes in Rat Ciliary Body Using Subtype-Selective Ligands

“…The affinity of BQ123 for the ETA receptor in this tissue is in the nanomolar region, similar to the affinity reported for a number of tissues including cardiac muscle , kidney (Karet, Kuc and Davenport, 1993), rat retina (de Juan et al, 1995) and rat heart (Peter and Davenport, 1996).…”

“…These results suggest that the ETB receptor present in all these tissues might belong to the same subtype of ETB receptors and differs from those present in canine spleen (Nambi et al, 1995) and in rat and pig heart (Peter and Davenport, 1996).…”

“…However, this ETB-ligand competes with low affinity in canine spleen (Nambi et al, 1995) and in porcine and rat heart (Peter et al, 1996). These discrepancies in the binding affinity for BQ3020, in addition with data from functional experiments (Shetty et al, 1993 ;Gardiner et al, 1994), have led to the suggestion that ETB receptors may be modified according to the tissues in which they are expressed within the same animal or between different species (Nambi et al, 1995 ;Peter and Davenport, 1996).…”

Impaired Stimulatory Effect of ETB Receptor on D₃ Receptor in Immortalized Renal Proximal Tubule Cells of Spontaneously Hypertensive Rats

“…The specificity of these antibodies had been reported [24][25][26][27][28] . RPT cells were treated with vehicle (dH 2 O), BQ3020 (Sigma, Co., St. Louis, Mo., USA) [29,30] , or an ETB receptor antagonist (BQ788; Sigma) [29,30] at the indicated concentrations and times. Immunoblotting was performed as reported, except that the transblots were probed with ETB (1: 300) or D 3 receptor antibodies (1: 250) [24][25][26][27][28] .…”

Blood pressure response to type A endothelin receptor antagonism in human obesity and diabetes mellitus

“…ET-1 blockade was achieved with BQ123 (Clinalfa, Basel, Switzerland), a high-affinity competitive inhibitor of ET-1 type A receptors. 5 Under the original study design, the outcome of interest was the effect of endothelin antagonism on leg vascular function. Therefore, BQ123 was infused into the femoral artery, with measurements made after 90 min exposure to 1 mmol/min, and again following a further 30 min exposure to 3 mmol/min.…”