Turnover of human tissue plasminogen activator (tPA) in rabbits

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.