Increase in the kinin levels in the bronchial washings after intravenous injection of leukotriene C4 in guinea pigs.
In guinea pig plasma, bradykinin (BK) was degraded mainly to des-Arg1-BK by an aminopeptidase-like enzyme, which was inhibited by 2-mercaptoethanol. Besides this degradation, BK was also hydrolyzed by kininase I and kininase II from C-terminal end to des-Arg9-BK, des-Phe8-Arg9-BK and Arg-Pro-Pro-Gly-Phe ([1-5] BK). The formation of des-9-BK was strongly blocked by DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGPA) and that of des-8,9-BK and [1-5] BK was inhibited by captopril. When guinea pigs were pretreated with a cocktail of 2-mercaptoethanol, MGPA and captopril, intravenous administration of leukotriene (LT) C4 (10 nmol/kg) caused an increase in the levels of free kinin in the bronchial washings of guinea pigs. This increase was accompanied with the increase in glandular-kallikrein activity, which could be inhibited by aprotinin. As BK is reported to induce both bronchoconstriction and bronchial secretion, the increased free BK induced by LTC4 might enhance the effect of LTC4.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Jin
H Y
HY
Katori
M
M
Sunahara
N
N
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001711:Biotransformation; D001920:Bradykinin / Q000031:analogs & derivatives / Q000097:blood*; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007705:Kinins / Q000378:metabolism*; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D008969:Molecular Sequence Data; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology*
D007705:Kinins; D013189:SRS-A; D008623:Mercaptoethanol; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D002216:Captopril; D015097:3-Mercaptopropionic Acid; D001121:Lysine Carboxypeptidase; D001920:Bradykinin