Proline in vasoactive peptides: consequences for peptide hydrolysis in the lung

• Published in: American journal of physiology. Lung cellular and molecular physiology 1999-02, Vol.276 (2), p.341-L350
• Main Authors: Merker, Marilyn P, Audi, Said H, Brantmeier, Becky M, Nithipatikom, Kasem, Goldman, Robert S, Roerig, David L, Dawson, Christopher A
• Format: Article
• Language: English
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.1999.276.2.l341

Departments of Anesthesiology, Pharmacology/Toxicology, and Physiology, Medical College of Wisconsin, Milwaukee 53226; Department of Biomedical Engineering, Marquette University, Milwaukee 53233; and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 To examine the hypothesis that trans isomers of bradykinin and [Gly 6 ]bradykinin are preferentially hydrolyzed by lung peptidases, we studied the fractional inactivation of these peptides in the perfused rat lung using a bioassay after a single-pass bolus injection and high-performance liquid chromatography after lung recirculation. In the bioassay studies, when the peptides passed through the lung, 25.6-fold more bradykinin or 7-fold more [Gly 6 ]bradykinin was required to elicit a contraction equivalent to that produced when the peptides did not pass through the lung. In the recirculation studies, hydrolysis progress curves with rapid and slow phases were observed, with a higher fraction of bradykinin than [Gly 6 ]bradykinin hydrolyzed in the rapid phase. Cyclophilin increased the hydrolysis rate during the slow phase for both peptides. Kinetic analysis indicated that the slowly hydrolyzed peptide fraction, presumably the cis fraction, was 0.13 for bradykinin and 0.43   for [Gly 6 ]bradykinin with cis - trans isomerization rate constants of 0.074   and 0.049 s 1 , respectively, consistent with published nuclear magnetic resonance studies. high-performance liquid chromatography; bradykinin; [6-glycine]bradykinin; lung peptidases; cis - trans isomerase; cyclophilin