NOVEL 31-AMINO-ACID-LENGTH ENDOTHELINS CAUSE CONSTRICTION OF VASCULARSMOOTH-MUSCLE

We have reported that human chymase specifically cleaves big endotheli ns (ETs) at the Try(31)-Gly(32) bond, and produces novel trachea-const ricting 31-amino-acid-length ETs, ETs(1-31). In this study, we investi gated the effect of synthetic ETs(1-31) on the contractile activity to ward porcine coronary arteries and rat aortae. Although ETs(1-31) exhi bited less potent vasoconstrictile activity in these tissues than al-a minoacid-length ETs(1-21), or a similar extent, ET-1(1-31) caused sign ificantly slower-developing and longer-lasting contraction than ETs(1- 21). The ETA receptor antagonist, BQ485, completely inhibited the acti vity of ET-1(1-31). The ETB receptor antagonist, BQ788, also inhibited the activity of ET-1(1-31) toward rat aortae more efficiently than th at ET-1(1-21). Therefore, trachea-constricting peptides ETs(1-31) play roles as vasoconstrictors in a different manner from ETs(1-21). (C) 1 998 Academic Press.