FUNCTIONAL AND AUTORADIOGRAPHIC STUDIES OF ENDOTHELIN-1 AND ENDOTHELIN-2 IN HUMAN BRONCHI, PULMONARY-ARTERIES, AND AIRWAY PARASYMPATHETIC GANGLIA

We compared the contractile potency and efficacy of two of the forms of endothelin (endothelin-1 and endothelin-2) on human bronchi and pulmonary arteries in vitro and examined the effects of sarafotoxin on the bronchial preparations. In addition, we used autoradiographic methods to investigate the location of binding sites for both forms of endothelin within human lung. Endothelin-1 (ET-1) was 2.5 times more potent than endothelin-2 (ET-2) in both the airway and vascular tissues, and both forms of the peptide were 5 times more potent in the isolated pulmonary artery than in the bronchial tissue. There were no differences in the magnitude of the contractions generated by ET-1 and ET-2 in either tissue type. Sarafotoxin also produced a contractile response in the bronchi that was equipotent to ET-1 but of a greater magnitude. Specific binding on the smooth muscle of bronchus, pulmonary artery, and alveolar walls to both ET-1 and ET-2 was detected in autoradiographic studies. In addition, binding sites for both forms of the peptide were localized to parasympathetic ganglia within the airways, where the presence of muscarinic receptors was also confirmed with [H-3]QNB. There appeared to be no difference between the endothelins in the location or the density of binding sites. These results indicate that endothelin may have a neuromodulatory role in the airways as well as a direct contractile action on the bronchial and arterial smooth muscle.