Characteristics of endothelin receptors in acutely rejecting transplanted lungs

Experiments were designed to characterize endothelin receptors in bronchi and parenchyma of transplanted lungs during acute rejection. Third-order bronchi from autografted or allografted lungs were either cut into rings and suspended in organ chambers for the measurement of isometric force or frozen for isolation of membrane proteins. Lung parenchyma was prepared for histology or isolation of membrane protein. The grade of rejection was 2.74+/-0.17 (n= 19) in allotransplanted lungs; evidence of infection was present in 58% of the transplanted lungs. In organ chamber experiments, endothelin 1 (which stimulates endothelin A receptors) caused comparable contraction of bronchi from autotransplanted and allotransplanted rejecting lungs. Endothelin 3 (which stimulates endothelin A and B receptors) caused contractions of bronchi from autotransplanted lungs which were not different from those caused by endothelin 1. In contrast, contractions caused by endothelin 3 were reduced in bronchi from rejecting allotransplanted lungs. The magnitude of contractions caused by endothelin 3 was reduced further when infection was present with rejection. Competitive inhibition of 125I-endothelin 1 by endothelin 3 was significant for a two-site binding model in membranes prepared from all bronchi and lung parenchyma. The total number of binding sites (Bmax) was reduced significantly in bronchi and parenchyma from rejecting lungs with or without infection. The relative proportions of high-affinity and low-affinity binding sites did not change. Affinities of both high- and low-affinity receptors were not altered with rejection. These results indicate that at least two subtypes of endothelin receptors are present on canine bronchial smooth muscle and parenchyma. The number of endothelin receptors associated with bronchial contractions is reduced with rejection of lung allografts.