Catabolism of hirudin and thrombin-hirudin complexes in the rat.
The metabolic fate of the anticoagulant protein, hirudin, and its complex with thrombin are presently unknown. Therefore we have labelled hirudin and human thrombin-hirudin complex with the residualizing label dilactitol-125I-tyramine (*I-DLT) in order to identify their tissue sites of catabolism in the rat. The rapid plasma clearance of hirudin after intravenous injection was unaffected by *I-DLT labelling, and by 2 h 6% or less of the injected dose remained in the blood. The majority (80.3 +/- 4.0%, n = 2) of *I-DLT-hirudin radioactivity recovered in tissues was found in kidney, and kidney was also at least 150 times more active in taking up hirudin, on a weight basis, than any other tissue examined (liver, spleen, skin, muscle, intestine, fat, lung). *I-DLT-hirudin which bound to thrombin was isolated by chromatography on concanavalin A-Sepharose; hirudin itself does not bind to concanavalin A. Radioactivity from thrombin-*I-DLT-hirudin was precipitable by anti-thrombin antibody and *I-DLT-thrombin-hirudin was precipitable by anti-hirudin antibody. By 1 h after injection of labelled thrombin-hirudin complexes, the recoveries of radioactivity from hirudin and thrombin in liver were comparable (38.6 +/- 3.0 and 36.4 +/- 4.1%, n = 3), whereas more radioactivity was recovered in kidney from hirudin than from thrombin (27.6 +/- 8.7 compared with 13.6 +/- 4.5%) and less was recovered in lung (0.4 +/- 0.2 compared with 17.7 +/- 2.9%). We conclude that hirudin is catabolized predominantly in kidney, whereas the thrombin-hirudin complex is catabolized by both liver and kidney.
Bichler
J
J
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208.
Baynes
J W
JW
Thorpe
S R
SR
D000818:Animals; D002846:Chromatography, Affinity; D003208:Concanavalin A; D004791:Enzyme Inhibitors; D005260:Female; D006629:Hirudins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000302:isolation & purification / Q000378:metabolism*; D014439:Tyramine / Q000031:analogs & derivatives
D004791:Enzyme Inhibitors; D006629:Hirudins; D003208:Concanavalin A; C049133:dilactitol tyramine; D013917:Thrombin; D014439:Tyramine