Structural Requirements of Sugars as Antagonists of the Vascular Response to Dextran in Rat Skin

Abstract

The increase in vascular permeability induced by dextran in rat skin is inhibited by the simultaneous intradermal administration of glucose and certain other sugars (Beraldo, Dias Da Silva & Lemos Fernandes, 1962). These sugars also prevent the local vascular changes produced by other polysaccharides (Poyser & West, 1965;Harris, Luscombe & Poyser, 1967) and inhibit the release of histamine in vitro by dextran from tissue mast cells (Goth, 1961;Beraldo et al., 1962;Dias Da Silva & Lemos Fernandes, 1965). In the present paper, an attempt has been made to determine the structural and stereospecific requirements of sugars for activity as antagonists of the dextran response. The mechanism of inhibition by these carbohydrates has also been investigated. METHODSInhibition by sugars and other agents of the vascular response to dextran in rat skin was studied using the method of Poyser & West (1965). Each antagonist was dissolved in dextran (1 mg/ml.) and injected intradermally, in volumes of 0.1 ml., into the shaved ventral abdominal skin of male hooded Lister rats (body weight about 200 g). Each rat received eight to ten intradermal injections immediately after the intravenous injection of azovan blue dye (7 mg/kg). Thirty minutes later the rats were killed, and the reaction to each injection was assessed by measuring the mean diameter of the blue area on the inner surface of the skin. The response given by dextran (100 jug) in the presence of each sugar or other agent was then expressed as a percentage of that found in its absence. From the log dose/inhibition curves, doses producing 50% inhibition (termed the ID50 values) were obtained. Each value shown in the tables is the mean and standard error of three experiments, each using at least three rats.

The Relationship Between Energy Metabolism and the Action of Inhibitors of Histamine Release

“…mean of 45 observations) compared with 49.6 + 1.6% from samples of the same cell suspensions incubated in glucose-free medium. This difference is consistent with the inhibition by glucose of dextran anaphylactoid reactions in rats described by Beraldo et al (1962) and Poyser & West (1968). Inhibition of dextran-induced release from cells incubated in either glucose-free or complete medium was calculated by reference to the appropriate control release corrected for the spontaneous histamine release which was the same in each medium (6.7 + 0.4%).…”

Histamine Release from Isolated and Intact Mast Cells of Rats

“…Similar results were obtained by Poyser and West [5] in the skin of R rats using dextran as the stimulant of increased vascular permeability. These re sults all suggest that BSA, Con A and dex tran induce histamine release from isolated periotneal mast cells of R rats by a similar mechanism.…”

Further Analysis of the Resistance of a Colony of Rats to Dextran

“…The dextran re ceptor in reactors appears to be activated by an endogenous agent which is not blood-borne. As a result of experiments involving carbohydrates as antagonists of intradermal dextran in reactor rats, Poyser and West [1968] concluded that there may be a stereospecific receptor for polysac charides in rat skin as the most active inhibitory monosaccharides such as glucose all contained the D-threo type of structure in their cyclic form. Galactose does not contain this type of structure and was a very weak in hibitor, and Hanahoe et al [1973] found that it also failed to inhibit the histamine release from isolated mast cells of reactor rats by dextran and PS.…”