Effects and specific binding sites of endothelin in human lung preparations

Abstract

Endothelin binding in human isolated lung membrane fractions revealed a single class of high affinity recognition sites with a K d of 1.33±0.15 nM and a B max of 9.61±1.44 pmol/mg protein. Endothelin inhibited [ 125I]endothelin binding with a K i of 1.90±0.15 nM whereas structurally unrelated compounds had no effect. Endothelin was a potent contractile agonist on human isolated pulmonary arterial (HPA) and venous (HPV) muscle preparations (pD 2 values: 9.64 and 10.36, respectively). Neither indomethacin (1 μM), nicardipine (0.01, 0.10, 1.0 μM) nor diltiazem (1, 10, 100 μM) altered the sensitivity of HPA to endothelin. Human isolated bronchial muscle preparations were less sensitive to endothelin than vascular tissues. These data suggest that pulmonary veins may be a major target for this constrictory peptide in the human lung.