(With the technical assistance of Miss J. E. Harthill) A-Carrageenans and K-carrageenans from samples of Chondrus crispus, carrageenan from Polyides rotundus and degraded carrageenan from Eucheuma spinosum have anticoagulant activity on intravenous injection in the rabbit. Anticoagulant activity appears to be caused by a general reaction with plasma protein. The undegraded carrageenans are acutely toxic on intravenous injection and form insoluble complexes with fibrinogen in neutral solution. Degraded carrageenan is very much less toxic and, like heparin, forms soluble complexes with fibrinogen. The A-carrageenans from C. crispus have higher sulphate content, consistently prolong the clotting time more, and are more toxic than the corresponding K-carrageenans. The differences in sulphate content between the various A-carrageenans, and between the carrageenans from the other seaweeds tested, do not correspond directly with differences in anticoagulant action and toxicity.HE carrageenans, which occur naturally in the red seaweeds, constitute T a closely related group of sulphated galactans. While displaying the biological properties of sulphated polysaccharides in general, quantitative differences exist between the members of the group and between the readily separated K-and A-carrageenans which are present in certain of the members. Houck, Morris & Lazaro (1957) examined unfractionated whole extracts of a number of seaweeds for anticoagulant activity which they found only in Gigartina acicularis. Hawkins & Leonard (1962, 1963) fractionated one Chondrus crispus carrageenan into its K-and A-components and found greater anticoagulant activity in the A-carrageenan which contained more ester sulphate than the K-carrageenan. Rees (1963) has suggested that A-carrageenan may be the biological precursor of K-carrageenan. Whole extracts of seaweeds might therefore be expected to vary in the relative content of K-and A-carrageenans and hence in anticoagulant activity. This may explain largely negative findings such as those of Houck & others (1957).We report a study of the anticoagulant activity of a group of carrageenans differing in ester sulphate content, molecular weight and source. Materials and methodsAnimals. Male New Zealand white rabbits (2-4 kg) were used. Food, but not water, was withheld for 18 hr before testing. Each animal acted as its own control and none was used more than once.Blood was allowed to drip freely into Pyrex glass tubes from a small incision made on the marginal vein of the shaved, warmed and solvent-cleaned ear. The first ml of blood was discarded.Control results were obtained from blood withdrawn immediately before injection of carrageenan ; test bloods were withdrawn 2 hr after the injection of carrageenan, or 0.5 hr in the heparin experiments. Preliminary experiments showed that the greatest anticoagulant effect of the carrageenans occurred 2 hr after injection while that for heparin occurred at 0.5 hr.
1. In anaesthetized dogs, various amounts of [(14)C]histamine were introduced into the lumen of a ligated intestinal loop or of the ligated stomach and the absorption of this histamine was studied by determining the radioactive histamine in the venous blood coming from the ligated part.2. After the introduction of 5-5000 mug [(14)C]histamine, into a loop of jejunum, or of 50 mug into a loop of duodenum, ileum or colon, radioactive histamine was detected in all eight successive 15 min samples of venous blood collected during 2 hr. The percentage recovery of the [(14)C]histamine in the blood during this period varied between 0.04 and 3.7.3. After the introduction of 10 mg [(14)C]histamine into the stomach, radioactive histamine was detected in all samples of gastric venous blood collected at various times during the following 4 hr.4. After the introduction of 50-5000 mug [(14)C]histamine into a loop of jejunum, radioactive histamine was also detected in the general arterial blood.5. When a jejunal loop was perfused through its artery with a dextransaline solution, the absorption of [(14)C]histamine from the lumen into the venous effluent was much greater than when the blood supply was kept intact.6. A large part of the [(14)C]histamine introduced into an intestinal loop was inactivated or destroyed either in the lumen or the wall since only a part was recovered in the venous blood, contents and wall of the loop at the end of 2 hr. When different amounts of [(14)C]histamine were introduced into a jejunal loop the recovery was shown to be dependent on the dose. With 5 mug it amounted to about 1% whereas with 5000 mug to 29-42%. The recovery of the [(14)C]histamine introduced into a perfused jejunal loop was greater.7. In dogs and cats large amounts of free histamine were found in the contents of the stomach 2 hr after a meat meal, and much smaller amounts in the contents of loops from the small intestine. The amounts found in the contents of loops from the colon varied greatly.8. In eighteen commercial dog and cat foods the free histamine contents were found to vary over fiftyfold, from 0.06 to 3.5 mg/100 g.9. The significance of the results is discussed in relation to the role of histamine as a humoral agent in the ;gastric' and ;intestinal phases' of gastric secretion.
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