Species variation in pulmonary endothelial aminopeptidase P activity

X. Chen, S. E. Orfanos, J. W. Ryan, A. Y.K. Chung, David C Hess, J. D. Catravas

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Abstract

Pulmonary endothelial aminopeptidase P (AmP) may be an important contributor to the inactivation of circulating bradykinin in certain species. To examine this possibility, we measured AMP activity in vivo and in vitro using Arg-Pro-Pro-[3H]benzylamide (3H-APPB) as substrate under conditions of first order enzyme kinetics. Utilizing multiple indicator dilution techniques, metabolism of 3H-APPB to Arg and Pro-Pro-[3H]benzylamide by AmP was not detectable during a single transpulmonary passage in anesthetized rabbits (n = 4), cats (n = 3) and pigs (n = 4). However, percent metabolism of 3H-APPB ranged from 54 to 63% in anesthetized rats (n = 6). In all experiments, the substrate remained within the vascular space and was thus accessible to endothelial and blood AmP only. At the same time, single-pass transpulmonary percent metabolism of [14C]benzoyl-Ala-Gly-Pro by endothelial-bound angiotensin converting enzyme was remarkably similar among rabbits, cats, rats and pigs (60-65%). In culture, V(max)/K(m) of AmP was 3 to 10 x 10-4 min-1 for human basal arterial and rabbit and bovine pulmonary arterial endothelial cell monolayers (2 x 105 cells). AmP activity in the supernatant of lung and kidney tissue (homogenized in saline containing 1-o-n-octyl-β-glucopyranoside) from rabbit, cat, pig and rat expressed as V(max)/K(m)(min-1) per (g wet tissue/ml) was 0.74, 2.25, 3.91 and 185.8 (lung), and 1.0, 3.7, 8.4 and 438.3 (kidney), respectively. Similarly, V(max)/K(m) values of AmP in plasmas of cat, dog, rabbit, pig, calf (serum), human and rat were 0, 0.016, 0.025, 0.068, 0.191, 0.237 and 3.53 min-1. These results suggest that 1) there are large interspecies variations in AmP activities of plasma, lung and kidney; 2) of the species studied, the rat contains the largest activities of AmP; and 3) AmP appears to be located on the luminal surface of the rat pulmonary endothelium.

Original languageEnglish (US)
Pages (from-to)1301-1307
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume259
Issue number3
StatePublished - Dec 1 1991

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Chen, X., Orfanos, S. E., Ryan, J. W., Chung, A. Y. K., Hess, D. C., & Catravas, J. D. (1991). Species variation in pulmonary endothelial aminopeptidase P activity. Journal of Pharmacology and Experimental Therapeutics, 259(3), 1301-1307.