Localization and characterization of endothelin-1 binding sites in the transplanted human lung.
The localization and characterization of endothelin-1 (ET-1) binding in sections of transplanted and control human lung tissues was investigated by in vitro autoradiography. Binding of [25I]ET-1 was saturable and specific, and demonstrated a single class of binding sites. Scatchard analysis of the data revealed a Kd of 0.52 +/- 0.15 nM and a Bmax of 61.17 +/- 4.5 amol/mm2 to normal lung parenchyma, and a Kd of 0.48 +/- 0.29 nM and a Bmax of 123.9 +/- 18.5 amol/mm2 to normal bronchial smooth muscle. In transplanted human lung, the binding characterizations were similar to those of normal lung. Scatchard analysis indicated high-affinity sites having a Kd of 0.8 +/- 0.19 nM and a Bmax of 153.6 +/- 9.2 amol/mm2 to lung parenchyma and a Kd of 0.59 +/- 0.21 nM and a Bmax of 141.77 +/- 14.6 amol/mm2 to bronchial smooth muscle. Binding in transplanted and control tissues was similar and was inhibited by co-incubation with an excess of unlabeled ETs (ET-1 > ET-2 > ET-3) but not by other unlabeled peptides. Binding was mainly localized to lung parenchyma, small blood vessels [muscular pulmonary artery (100-500 mm) and bronchial blood vessels], pulmonary veins, and bronchial smooth muscle. The specific binding in small blood vessels was lower in transplanted lung than in control lung. Less specific binding was found in elastic pulmonary vessels than in small blood vessels in both transplanted and control lungs. No binding was found in the cellular perivascular infiltrates of the transplanted lung. These results suggest that ET-1 acts intrinsically and that high-affinity receptors for it exist in transplanted lung both in the parenchyma and bronchial smooth muscle.
Zhao
Y D
YD
Department of Histochemistry, Royal Postgraduate Medical School, London.
Springall
D R
DR
Hamid
Q
Q
Yacoub
M H
MH
Levene
M
M
Polak
J M
JM
D000293:Adolescent; D000328:Adult; D001345:Autoradiography; D001665:Binding Sites; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000737:chemistry*; D016040:Lung Transplantation; D008875:Middle Aged; D017466:Receptors, Endothelin / Q000032:analysis*
D016232:Endothelins; D017466:Receptors, Endothelin