CHARACTERISTICS OF ENDOTHELIN RECEPTORS IN ACUTELY REJECTING TRANSPLANTED LUNGS

Experiments were designed to characterize endothelin receptors in bron chi and parenchyma of transplanted lungs during acute rejection. Third -order bronchi from autografted or allografted lungs were either cut i nto rings and suspended in organ chambers for the measurement of isome tric force or frozen for isolation of membrane proteins. Lung parenchy ma was prepared for histology or isolation of membrane protein. The gr ade of rejection was 2.74+/-0.11 (n=19) in allotransplanted lungs; evi dence of infection was present in 58% of the transplanted lungs. In or gan chamber experiments, endothelin 1 (which stimulates endothelin A r eceptors) caused comparable contraction of bronchi from autotransplant ed and allotransplanted rejecting lungs. Endothelin 3 (which stimulate s endothelin A and B receptors) caused contractions of bronchi from au totransplanted lungs which were not different from those caused by end othelin 1. In contrast, contractions caused by endothelin 3 were reduc ed 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 I-125-endotheli n 1 by endothelin 3 was significant for a two-site binding model in me mbranes prepared from all bronchi and lung parenchyma. The total numbe r of binding sites (B-max) was reduced significantly in bronchi and pa renchyma from rejecting lungs with or without infection. The relative proportions of high-affinity and low-affinity binding sites did not ch ange. Affinities of both high- and low-affinity receptors were not alt ered 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 br onchial contractions is reduced with rejection of lung allografts.