title: Plasma protein binding and endothelial enzyme interactions in the lung.
abstract: The influence of plasma albumin binding of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP) on BPAP hydrolysis by pulmonary endothelial ACE was studied in isolated rabbit lungs perfused with a salt solution containing either 5% bovine serum albumin (BSA) or 5% dextran. The single-pass indicator-dilution method was used to measure the fraction (M) of [3H]BPAP hydrolyzed. Lung M was greater with albumin-free perfusate than when BSA was present. M decreased as the time (ti) that the BPAP was in contact with the BSA before reaching the lung was increased, suggesting that some BSA binding sites for BPAP were not in equilibrium during bolus transit through the lungs. The M vs. ti data were correlated using a model incorporating both rapid and slow binding kinetics of BPAP and BSA. For the slow BPAP-BSA interaction, the dissociation rate constant was approximately 0.015 s-1, and the fraction of the BPAP bound to these slowly equilibrating sites at equilibrium was approximately 22%. The results indicate that transient plasma protein binding kinetics can affect lung BPAP hydrolysis.
authors.affiliation: Medical College of Wisconsin, Milwaukee 53226.
authors.forename: J H
authors.initials: JH
authors.lastname: Linehan
authors.forename: C A
authors.initials: CA
authors.lastname: Dawson
authors.forename: R D
authors.initials: RD
authors.lastname: Bongard
authors.forename: T A
authors.initials: TA
authors.lastname: Bronikowski
authors.forename: D L
authors.initials: DL
authors.lastname: Roerig
mesh_terms: D000818:Animals; D004727:Endothelium / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D012710:Serum Albumin, Bovine; C029689:benzoylphenylalanyl-alanyl-proline; D007703:Peptidyl-Dipeptidase A