Andres Goth

Phosphatidylserine: selective enhancer of histamine release.

Phosphatidylserine, in contrast with other phospholipids, markedly enhanced histamine release from rat peritoneal mast cells induced by dextran or protein antigens. This enhancing effect was selective for dextran and protein antigens and did not extend to the action of compound 48/80 or chymotrypsin. These findings suggest a role for phosphatidylserine in the response of mast cells to antigens.

Effect of Drugs on Mast Ceils

Publisher Summary The use of drugs for the study of mast cell function has not been impressive so far. With a few exceptions, little is known about the influence of massive depletion of mast cells on the physiological processes and even less about the effect of drug-induced stimulation of mast cell activities on various functions, normal or pathological. Among the many methods used in the study of mast cells, some are more useful in relation to drug effects than others. The methods are generally of two types based on morphology or on the measurement of histamine release. The latter, in turn, may be studied, using the whole animal, an organ, or isolated suspended mast cells, usually obtained from the rat peritoneum. The majority of drugs commonly referred to as histamine releasers or liberators may properly be looked upon as drugs acting on the mast cell. Several new drugs and new concepts have been added to this chapter of pharmacology. Despite the fact that there are so many drugs that act on the mast cell, there have been few attempts at bringing this pharmacologic information together in an organized manner. This chapter discusses meaningful advances in this field from a pharmacologic point of view. Emphasis is placed on those reports that allow a rational classification of drugs that act on the mast cell, on the species-dependent responses to drugs, and relationship of metabolism to drug effects.

Pathogenesis of experimental cholera: choleragen-induced rat foot edema; a method of screening anticholera drugs.

Summary This preliminary study suggests that the rat foot edema test may provide a useful means of screening pharmacological agents potentially capable of preventing or reversing the specific metabolic lesions induced by cholera enterotoxin (choleragen). The first inhibitor selected for study, cyclo-heximide, prevented or delayed the onset of choleragen-induced edema in the rat foot test and also prevented the development of choleraic diarrhea in the infant rabbit assay. However, it did not alter the course of the established lesion in the rat foot. These observations suggest that a choleragen-induced, host-produced protein mediator may be involved. Additional studies, involving this model, directed toward understanding the pathogenic mechanism of cholera toxin and to develop potentially more effective methods of treatment of cholera patients, are in progress. We wish to thank Miss Mary Knoohuizen for her assistance in helping to set up these assays. Support was provided by a grant, 1 R22 AI08877-01, from the National Institute of Allergy and Infectious Diseases.

Tissue thromboplastins and histamine release from mast cells

Abstract The effect of tissue thromboplastins on histamine release from rat peritoneal mast cells was investigated. Lung thromboplastin (Aplastin) and Russell Viper Venom (Stypven) were highly effective as histamine releasers. Brain thromboplastin was less active by itself but became potent upon the addition of dextran or ovomucoid, known “anaphylactoid” agents in the rat. The possibility is suggested that thromboplastin-like tissue factors may be involved in some types of histamine release. They may also play a role in the “anaphylactoid” reaction of rats to polymeric compounds.

Interaction of carbohydrates and anti-inflammatory drugs with mast cells in the rat

Abstract Certain sugars, especially 2-deoxyglycose, can block inflammation produced by dextran or ovomucoid in the rat. This anti-inflammatory actions of sugars is well correlated with their ability to inhibit degranulation and histamine release of mast cells by dextran or ovomucoid in vitro or in vivo . Because the same sugars do not inhibit the action of compound 48/80, special receptors have been postulated for the polysaccharide. In an extension of this work, a number of anti-inflammatory drugs were tested against the effects of dextran and compound 48/80 on rat (Wistar) peritoneal mast cells by using inhibition of histamine release as a measure of their potency. All anti-inflammatory drugs tested, such as sodium salicylate, phenylbutazone, hydrocortisone sodium succinate, and colchicine, were much more active in blocking the action of dextran than that of compound 48/80. The preferential effect of sodium salicylate on the systemic action of dextran as contrasted with that of compound 48/80 was demonstrable in vivo . The greater susceptibility of the dextran effect to the anti-inflammatory drugs points to a different mode of action of the polysaccharide as compared with compound 48/80. Since edema produced by the polysaccharide carrageenin is also highly susceptible to inhibition by anti-inflammatory drugs, this relationship may reflect a similarity in the mode of action of polysaccharides.

MECHANISMS OF HISTAMINE RELEASE BY POLYMERIC COMPOUNDS

Publisher Summary This chapter discusses the mechanisms of histamine release by polymeric compounds. It also describes the effect of dextran on histamine release from peritoneal cells. Dextran alone even at a concentration of 6 mg/ml had no effect, because the amount of histamine appearing in the supernatant was the same as in control tubes. Increasing amounts of brain acetone powder supernatant alone caused increasing amounts of histamine to be released. The addition of dextran to cells pretreated with brain powder supernatant caused a considerable increase in the amount of histamine released. It was found important in these experiments to add the brain powder supernatant just before the dextran. The two solutions could be mixed and added together, a procedure that tended to increase somewhat the amount of histamine released. In some experiments, ovomucoid was substituted for dextran with very similar results. On the other hand, polivinylpyrrolidone had no effect. Preliminary experiments indicate that pieces of rat skin extracted with acetone and homogenized in saline give results similar to those with brain powder.

Some Observations on Nature of Refractoriness to Histamine Liberators.

Summary The administration of a series of graded doses of compound 48/80 produces a refractory state to the histamine liberating action of this cornpound. This refractory state appears to be effected by a means other than that of depletion of available histamine body stores.