Action of Protamine on Production and Activity of Heparin-induced Clearing Factor. ∗

Abstract

Conclusions

(1) Samples of plasma taken from rats one to 3 minutes after they received an intravenous injection of protamine will inhibit clearing factor. Degree of inhibition varies with dose given, but even with doses as high as 10 mg no inhibition can be detected in the plasma 4 minutes after injection. An intravenous dose of 5 mg of protamine inhibited release of clearing factor for a period of more than 2 hours. It would seem that protamine which has been so quickly removed from the circulation, has been deposited at sites of clearing factor release. The simplest explanation, but by no means the only one, would be to assume that the site of clearing factor release is the endothelial lining of the vessels. This explanation would be in support of the hypothesis proposed by Robinson and French (8). (2) With intraperitoneal injections of protamine, inhibition of clearing factor release was detected in some animals within 5 minutes, whereas inhibitory activity was not detected in plasma until 30 to 60 minutes after injection, if at all. This was probably due to the fact that protamine was removed from the circulation almost as rapidly as it entered, and its removal blocked release of clearing factor. (3) Experiments in which protamine was injected daily for periods of 2 weeks indicated that the reported increase in atheromatous plagues (10) was probably not attributable to any prolonged impairment in clearing factor production. There would however be daily periods of from 2 to 4 hours immediately after each injection when there would be an impairment and this could be a contributing factor. (4) The increased ability to release clearing factor in animals adapted to cold environment may be associated with the general increase in metabolic rate. This increase in level of enzyme activity brought on by a physiological change encourages the thought that it has indeed a physiological function.