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.
Lebel
N
N
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
D'Orléans-Juste
P
P
Fournier
A
A
Sirois
P
P
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D008666:Metalloendopeptidases; D015244:Thiorphan / Q000494:pharmacology
D016232:Endothelins; D006020:Glycopeptides; D015244:Thiorphan; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon