Pulmonary metabolism of bradykinin analogues and the contribution of angiotensin converting enzyme to bradykinin inactivation in isolated lungs.
1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of both analogues on guinea-pig ileum was potentiated (2.5-3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4-5 fold). 4 Like bradykinin, the 8-homo Phe analogue was extensively inactivated (greater than 90%) in a single passage through the pulmonary circulation of guinea-pig or rat isolated lungs and this inactivation was prevented by pre-treatment of the lungs with BPP9a. 5 The 7-homo Pro analogue was inactivated to a lesser degree in guinea-pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a. 6 It is concluded that the 8-homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7-homo Pro analogue is not a substrate. 7 There is about four times as much dipeptidylcarboxypeptidase activity in guinea-pig isolated lungs as there is in rat isolated lungs.
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin