CONTRACTILE ENDOTHELIN-B (ETB) RECEPTORS IN HUMAN SMALL BRONCHI

Endothelins (ETs) are a family of novel regulatory peptides and variou s lines of evidence suggest an important role for ETs in regulating pu lmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA re ceptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved method ology was used which enables in vitro studies of small human bronchi d own to a diameter of 05-1.0 mm. Using the new methodology we have trie d to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue remov ed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 an d ET-3 elicited strong concentration-dependent contractions of the hum an small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed t he same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, re vealed that the effect of the ETB agonist was, in all respects, simila r to the responses induced by the ETs. PD 145065, a combined ETA/ETB r eceptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate m easurements can be made in vitro on small human bronchi and all presen t data are in favour of an ETB receptor mediating endothelin-induced c ontraction of human bronchi smaller than 1.0 mm.