Enzymes in normally perfused and ischaemic dog hearts which release a substance with kinin like activity.
The presence of amidases cleaving the tripeptide VAL.LEU.ARG.pNA, and liberating from human plasma kininogen substance(s) able to contract uterine smooth muscle and to lower blood pressure (uterus contracting and hypotensive activity), has been demonstrated in vascular and muscle tissues from normally perfused and ischaemic areas of dog hearts. Studies were carried out on blood free preparations of coronary arteries and veins and normally perfused and ischaemic ventricle. All the tissues were found to contain both acid optimum (pH 6) and alkaline optimum (pH greater than 9) enzymes forming uterus contracting substance (UCS, bioassayed on isolated uterus of rats in oestrus), the highest levels of both activities being found in arterial tissues and the least in ventricle. Enzyme levels in ischaemic or normally perfused ventricle did not differ significantly. Gel filtration (Sephacryl, S-300) of coronary artery extracts gave one peak each of acid optimum enzyme with a molecular weight of 38,300 +/- 800 daltons and alkaline optimum enzyme with a molecular weight of 92,100 +/- 4000 daltons. Both acid and alkaline enzyme fractions cleaved the tripeptide substrate with pH optima identical to those for UCS formation. The acid optimum activity, both of UCS formation and tripeptide cleavage, was inhibited by pepstatin but not by aprotinin or soybean trypsin inhibitor (SBTI). The alkaline optimum activity was inhibited by aprotinin and SBTI but not pepstatin. Both acid and alkaline optimum enzymes released a hypotensive agent from a plasma protein substrate. The molecular weight and response to inhibitors of the acid optimum enzyme were similar to a cathepsin, and those of the alkaline optimum enzyme were similar to plasma kallikrein.
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
I J
IJ
Zeitlin
S O
SO
Fagbemi
J R
JR
Parratt
D000818:Animals; D001681:Biological Assay; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000201:enzymology*; D003331:Coronary Vessels / Q000201:enzymology; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D007705:Kinins / Q000096:biosynthesis*; D009206:Myocardium / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D014599:Uterus / Q000187:drug effects
D007705:Kinins; D011480:Protease Inhibitors