title: Measurement of angiotensin converting enzyme inhibitors in serum by radioinhibitor binding displacement assay.
abstract: The principle of enzyme radioinhibitor binding displacement was developed to measure the concentration of angiotensin converting enzyme (ACE) inhibitors in rat serum. 125I MK351A, a tyrosyl derivative of enalaprilic acid, and a potent ACE inhibitor, bound in a concentration and time dependent manner to ACE. Binding of 125I MK351A to rat serum ACE was reduced in a concentration dependent manner in vitro by the ACE inhibitors MK521 (lisinopril), S9780, and Ro 31-3113-000 (Cilazapril diacid). This relationship was used to measure MK521 and S9780 in rat serum four hours after oral gavage with MK521, S9490-3 the prodrug ester of S9780, at 1, 2 and 4 mg/kg, or 1/2 hour after intraperitoneal injection of Ro 31-3113-000 (0.0125-0.7 mg/kg). Serum MK521 concentrations, estimated by radio inhibitor binding displacement, and radioimmunoassay, correlated well (r = 0.94, N = 9, P less than 0.001). Serum MK521, S9780 and Ro 31-3113-000 concentrations measured by radioinhibitor binding displacement assay were dose related, and inversely related to serum ACE enzymatic activity. The radioinhibitor binding displacement assay method using 125I MK351A as a ligand for ACE has application to the measurement of any competitive inhibitor of ACE.
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D017315:Cilazapril / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000378:metabolism*; D004656:Enalapril / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D007457:Iodine Radioisotopes; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011724:Pyridazines / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007457:Iodine Radioisotopes; D011724:Pyridazines; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D017315:Cilazapril; D004656:Enalapril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; C045980:cilazaprilat