(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.
The inhibition of the peptic activity of human gastric secretion by undegraded and degraded carrageenans of similar sulphate content has been examined over the pH range 1.5–3.75. Inhibition by degraded carrageenan is constant throughout this range, but inhibition by undegraded carrageenan decreases between pH 2.5 and 3.25, when a lower level is established. The inhibition by both types of carrageenan is caused by substrate‐inhibitor interaction. The differences in degree of inhibition and the effect of pH on the inhibition by undegraded carrageenan appear to originate in the differing natures of the substrate‐inhibitor complexes formed by degraded and undegraded carrageenans.
Sulphated polysaccharides reduce the proteolytic activity of pepsin principally by reacting with the substrate rather than with the enzyme ; and the complex so formed is protected by the polysaccharide from digestion.THE claim by Babkin and Komarov (1932) that the "mucoitin-and chondroitin-sulphuric acid" components of gastric mucus are capable of diminishing peptic activity without altering the level of free acidity, and the subsequent interest in pepsin as a possible ulcerogenic factor received support from results (Matzner and Windwer, 1937 ;Schiffrin, 1940 ;Schiffrin and Warren, 1942) indicating that hydrochloric acid alone was not ulcerogenic but that pepsin, in the presence of hydrochloric acid at pH 1.1-1-5 (Schiffrin and Warren, 1942) was so. In the guineapig treated with large doses of histamine, Watt (1959) showed that the primary aetiologic factor in the initiation of the acute ulcerative process is the acid gastric juice. He claimed that the acidity was not as important as the excessive production and prolonged action of the acid gastric juice.Antacid substances will inactivate pepsin by raising the pH and Shoch and Fogelson (1942) claimed that with the substances tested this was related to their influence on the acidity of the digest. Sodium lauryl sulphate, on the other hand, inhibited pepsin at high dilution without change in pH and increased the survival time of dogs given histamine.The anionic properties of sodium lauryl sulphate are similar to those of sulphated polysaccharides and both will engage in salt formation with protein at or below the isoelectric point of the protein. Levey and Sheinfeld (1954) studied the inhibition of proteolytic action of pepsin by some sulphated polysaccharides, finding that in vivo and in vitro inhibition of peptic digestion occurred and they proceeded to show that oral chondroitin sulphate reduced the incidence of gastric ulcers in the Shay rat. These authors believed their results to indicate that the sulphated polysaccharide combined with the enzyme to form an inactive complex or one with reduced activity.
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