K. Hisaki et al., CONVERSION OF BIG ET-1 IN THE RAT LUNG - ROLE OF PHOSPHORAMIDON-SENSITIVE ENDOTHELIN-1-CONVERTING ENZYME, The American journal of physiology, 266(2), 1994, pp. 80000422-80000428
We examined conversion of Big endothelin-1 (ET-1) to mature ET-1 and p
resser action during perfusion of the isolated perfused rat lung with
Big ET-1. Big ET-1 caused a concentration-related increase in perfusio
n pressure and the presser molar potency of the peptide was fivefold l
ess than that of ET-1. Presser responses to Big ET-1 were accompanied
by an increase in immunoreactive-ET (IR-ET) levels in the perfusate an
d in the lung tissues. Pretreatment with phosphoramidon (10(-4) M), a
metalloproteinase inhibitor, markedly suppressed the presser action an
d increment in IR-ET in the tissues. Unexpectedly, the amount of IR-ET
in the perfusate during perfusion of Big ET-1 was not influenced by p
hosphoramidon treatment. On the other hand, chymostatin, an inhibitor
of chymotrypsin-like enzymes, effectively suppressed IR-ET levels in t
he perfusate; however, this enzyme inhibitor was without effect on the
presser action of Big ET-1 or on the increase in IR-ET levels in lung
tissues. We tentatively conclude that the phosphoramidon-sensitive co
nversion of Big ET-1 to ET-1 is linked to the presser action of Big ET
-1 in the isolated perfused rat lung. In addition, it seems likely tha
t chymostatin-sensitive conversion of Big ET-1 to ET-1 does not play a
major role in the conversion of the precursor to the mature form. We
propose that IR-ET present in the tissues rather than that in the perf
usate is a better indicator of the functional conversion of Big ET-1 i
n the rat lung.