CHARACTERIZATION OF THE ENDOTHELIN-CONVERTING ENZYME IN GUINEA-PIG UPPER BRONCHUS

We studied the pharmacologic effects of big endothelin-1 (big ET-1), big endothelin-2 (big ET-2), and big endothelin-3 (big ET-3), and characterized the enzyme involved in the conversion of the three peptides in guinea pig upper bronchus (GPUB). ET-1, ET-2, and ET-3 (0.1-300 nM) elicited similar concentration-dependent contractions of GPUB. Big ET-1 and big ET-2, but not big ET-3, also elicited potent concentration-dependent contractions of GPUB. The conversion of big ET-1 to ET-1 in the GPUB is sensitive to phosphoramidon but not to thiorphan or captopril. Phosphoramidon inhibited the conversion of big ET-2 to ET-2, thiorphan had minimal effect, and captopril was without effect. These results suggest that the putative endothelin-converting enzyme (ECE) is involved in the conversion of big ET-1 to ET-1 in GPUB and the conversion of big ET-2 to ET-2 by a nonselective enzymatic process.