Presystemic bradykinin metabolism in sheep and rat nasal homogenates.
Bradykinin (BK) and its fragments BK(1-8), BK(1-7), and BK(1-5) were incubated with sheep nasal homogenates to investigate the extent of peptide metabolism within the nasal mucosa. The products for both bradykinin and BK(1-8) degradation were found to be BK(1-7) and BK(1-5). BK(1-7) was metabolized to BK(1-5) alone. The patterns of degradation suggest that the Pro7-Phe8 bond of bradykinin was hydrolyzed first, then BK(1-7) was further hydrolyzed to form BK(1-5). The metabolism of bradykinin in rat nasal homogenates and plasma was also investigated. BK(1-5) was the only metabolite measurable in the rat nasal homogenates, likely due to the activity of an endopeptidase. The reduction in the bradykinin degradation rate resulting from the inhibition of angiotensin converting enzyme (ACE) or carboxypeptidase N indicates that these enzymes participate in mucosal bradykinin metabolism to some degree. In comparison, the products of bradykinin hydrolysis in rat plasma were found to be BK(1-8), BK(1-7), and BK(1-5). These results indicate that the enzyme populations or/and activities vary significantly between different species and between different tissues within the same species. Although significant aminopeptidase activities were detected in the sheep nasal homogenates, bradykinin was not affected by their presence, since the N-terminal sequence of bradykinin is not susceptible to hydrolysis by most aminopeptidases.
Chung
F Y
FY
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Donovan
M D
MD
D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000493:pharmacokinetics*; D004789:Enzyme Activation; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013997:Time Factors
D001920:Bradykinin