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Clearance of human desaminotyrosyl fibrinopeptide a from the rat circulation: Role of kidney and proteolytic enzymes

1982; Elsevier BV; Volume: 26; Issue: 2 Linguagem: Inglês

10.1016/0049-3848(82)90016-0

1879-2472

David A. Lane, M Siodlak, Elizabeth Thompson, T G Allen-Mersh,

Cancer-related gene regulation

An investigation has been carried out of the elimination of fibrinopeptide A (FpA) from the rat circulation. 125I labelled desaminotyrosyl human FpA (125I-FpA) was injected into three groups of rats. These were (a) control rats (n = 9), (b) rats in which bilateral nephrectomy was performed (n = 10) and (c) rats which had acute bilateral ligation (n = 6). In the control rats elimination proceeded in a biphasic exponential manner. A fast initial clearance had a half life of less than 2 mins and this was followed by a slower component with an estimated half life of 51 mins. The fast component was caused by equilibration of the peptide throughout intra and extravascular spaces and the slow component reflected the action of catabolic processes once equilibration was attained. Nephrectomized rats had a similar initial fast clearance but the estimated half life of the slow component was 73 mins and also 10% less peptide was eliminated at a given time once equilibration had been achieved. The difference in half lifes of slow components of control and nephrectomized rats was not significant, while the difference in amount of excreted peptide was significant (p < 0.05) at each time point following equilibration. Rats with ligated ureters had almost identical clearance curves to nephrectomized rats (half life of slow component 73 mins), strongly suggesting that FpA is difectly filtered by the kidney. Blood samples withdrawn from control or nephrectomized rats at the completion of the experiments contained intact FpA and a major degradation fragment demonstrable by gel filtration on G10 Sephadex. A similar degradation could be elicited by in vitro incubation of 125I-FpA with fresh citrated blood. Urine also degraded 125I-FpA in vitro or in vivo to fragments, one of which was of similar molecular size to that produced in blood. It is concluded that proteolytic enzymes in blood degrade FpA which is then in part directly eliminated from the circulation by the kidneys: further degradation may then occur in the urine. The previously reported half life of FpA is a measure of its equilibration rather than of its catabolism.