title: Turnover of human tissue plasminogen activator (tPA) in rabbits.
abstract: The turnover of purified tissue plasminogen activator (tPA) from two different manufacturers was compared in rabbits. The first was melanoma derived one-chain tPA and the second was recombinant two-chain tPA. No differences were noted between the two products. A biphasic disappearance curve was observed for the protein (125Iodine labelled). The first phase was extremely rapid with a T1/2 of 0.59-0.89 min; the secondary phase had a T1/2 of 10-12 min. tPA accumulated rapidly in the liver (44% at twenty min) and appeared to be degraded as demonstrated by the increase in plasma of low molecular weight material which was also TCA soluble. Fractionation of purified recombinant two-chain tPA on a Dupont GF-250 column yielded two peaks of protein (Peak 1 and Peak 2) and the turnover of each in rabbits was compared.
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism*; D013329:Structure-Activity Relationship; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000378:metabolism*; D014238:Trichloroacetic Acid / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014238:Trichloroacetic Acid; D010959:Tissue Plasminogen Activator