THE DISTRIBUTION AND DENSITY OF RECEPTOR SUBTYPES FOR ENDOTHELIN-1 INPERIPHERAL LUNG OF THE RAT, GUINEA-PIG AND PIG

1 Quantitative autoradiographic studies were conducted to determine th e distributions and densities of endothelin-A (ET(A)) and ET(B) recept or subtypes in peripheral lung alveolar wall tissue of the rat, guinea -pig and pig, with a view to assessing the potential suitability of th ese tissues as models for investigations of ET receptor function in hu man alveolar tissue. 2 High levels of specific [I-125]-ET-1 binding we re detected in peripheral lung components from all three species teste d. In mature porcine alveolar wall tissue, specific binding increased in a time-dependent manner to a plateau, consistent with the previousl y described pseudo-irreversible binding of this ligand to a finite pop ulation of specific binding sites. 3 [I-125]-ET-1 was associated speci fically with both ET(A) and ET(B) binding site subtypes in alveolar wa ll tissue of foetal pig lung as early as 36 days gestation, raising th e possibility of a functional role for ET-1 in lung development. In ad dition, both ET(A) and ET(B) binding site subtypes were detected in al evolar wall tissue and in peripheral airway smooth muscle of mature lu ng parenchyma from all three species. However, the binding subtype pro portions differed in these tissues. For example, in porcine peripheral bronchial smooth muscle, ET(A) sites apparently predominated, whereas ET(A) sites constituted the major subtype detected in alveolar wall i n this species. These data suggest significant shifts in ET receptor s ubtype expression at different levels in the respiratory tract. 4 ET b inding site subtype proportions in the alveolar wall also differed mar kedly between species. In rat lung alveoli, ET(A) and ET(B) sites were detected in similar proportions (52+/-3% and 43+/-5% respectively). I n contrast, in guinea-pig peripheral lung, ET(B) binding sites clearly predominated, constituting approximately 80% of total specific bindin g, with ET(A) sites accounting for only 12%. Porcine alveolar wall tis sue also contained a mixture of these ET receptor subtypes, with ET(A) and ET(B) binding comprising 23+/-3% and 65+/-1% respectively of the total population of specific binding sites detected. These latter prop ortions are similar to values previously obtained in human peripheral lung tissue, suggesting that porcine lung might be a useful model of t he human peripheral lung in subsequent studies of the functions of the se pulmonary ET receptor subtypes.