Histaminasefreisetzung beim Kaninchen durch Heparin, andere Polyanionen und Protamin

Summary

The effects of heparin, some polyanions, and protamine on histaminase activity in plasma and in different organs of the rabbit were investigated.

• 1. Histaminase activity in plasma increases after injection of heparin in doses of 500 U/kg or more. The effect is approximately 25 times lower than that seen in the guinea pig with the same dose of heparin.

• 2. The release of the enzyme in slower in rabbits than in guinea pigs. Two peaks of activity were observed at 15 and 60 min, respectively, after heparin injection. The activity of the first peak was higher at pH 6.7 than at pH 7.4, while the reverse was true for the second peak. Under optimal pH conditions, the activity of the second peak reached a higher value than that of the first one. Incubation of plasma with EDTA-Na₂ abolished the first peak whereas the second was not affected.

• 3. Release of histaminase by heparin is blocked by protamine in doses of 10 mg/kg or more at both peaks.

• 4. The increase of the histaminase activity in plasma after heparin is accompanied by a significant decrease of activity in the intestinal mucosa; in liver the decrease of enzyme activity is small in contrast to that observed in the guinea pig. The kidney is not involved in the release of histaminase.

• 5. An increase of histaminase activity is elicited by other polyanions. Relatively high doses, however, are required: 60 mg/kg dextran N 500, 5 mg/kg dextran N 10, 100 mg/kg polyethylensulfonate, and 5 mg/kg pentosanpolysulfate being the minimal doses.

  The release of histaminase öfter these drugs showed only one peak and the optimum pH for the activity was 7.4.

• 6. Protamine leads to increased histaminase activity in plasma when given in doses more than 6 times higher than is necessary for inhibiting the heparin effect on the enzyme activity.