[Mediators of the allergic reaction. Slow reacting substance (SRS-A)].
The slow reacting substance of anaphylaxis (SRS-A) belongs to a group of substances which produce a slow progressive and sustained contraction of some smooth muscles. It is released by the interaction of the antigen with certain antibodies; in humans through the interaction with the IgE or reagine. The SRS-A is a heat-labile sustance, chemically unstable, of an acid character, with a low molecular weight. It is not destroyed by the action of proteolytic enzymes. Its molecular structure has not yet been elucidated. It is not found accumulated in the cells but synthesized and released by some white cells mainly by sensitized mast cells and polymorphonuclear leukocytes after challenging with the specific antigen. The SRS-A is a powerful pharmacodynamic agent, it produces contraction of the bronchial smooth muscle in doses of nanograms. It probably plays a predominant role in the physiopathology of asthma. The chain of chemical reactions elicited by antigen-antibody interaction does not end with the release of SRS-A and the other mediators (histamine, eosinophil chemotactic factor of anaphylaxis, ECF-A), on the contrary, these mediators especially SRS-A induce the release of prostaglandins of type E (PGE1 and PGE2) which produce bronchodilatation and inhibit the release of SRS-A itself, perhaps being a selfregulating mechanism. The PGF2a, on the other hand, produces bronchoconstriction. The release of SRS-A is also inhibited by the action of diethyl-carbamazine and especially by sodium chromoglicate and compound AH-7725. From the biochemical point of view it is found that the antigen Igells, a serine esterase, initiating several chemical reactions whose consequence is a decrease in the cAMP concentration. This reduction in the cAMP intracellular level is followed by synthesis and excretion of the SRS-A as well as by the aggregation of the microtubules and excretion of the stored histamine. The PGE (1 and 2) acting on one type of membrane receptor and the beta-agonist catecholamines on another produce a common phenomenon: the activation of the adenylcyclase whcih produces the increase of the concentration of cAMP and inhibits the release of mediators of the anapylactic reaction. The parasympathetic system through its chemical mediator acethylcholine, by a mechanism in whcih adenycyclase is not involved is also capable of stimulating the release of histamine and SRS-A. Something similar happens with PGF2a. In conclusion, self-regulatory mechansims for the release of mediators of the anaphylactic reactions may exist. The "perpetuation" of an asthamtic reaction would signify a failure of these self-regulatory mechanisms due to, for example, to a temporary block of the beta-adrenergic receptors, overstimulation of the alfa-receptors or insufficient production of PGE or a transformation of the PGE in PGF.
[Mediators of the allergic reaction. Slow reacting substance (SRS-A)]. The slow reacting substance of anaphylaxis (SRS-A) belongs to a group of substances which produce a slow progressive and sustained contraction of some smooth muscles. It is released by the interaction of the antigen with certain antibodies; in humans through the interaction with the IgE or reagine. The SRS-A is a heat-labile sustance, chemically unstable, of an acid character, with a low molecular weight. It is not destroyed by the action of proteolytic enzymes. Its molecular structure has not yet been elucidated. It is not found accumulated in the cells but synthesized and released by some white cells mainly by sensitized mast cells and polymorphonuclear leukocytes after challenging with the specific antigen. The SRS-A is a powerful pharmacodynamic agent, it produces contraction of the bronchial smooth muscle in doses of nanograms. It probably plays a predominant role in the physiopathology of asthma. The chain of chemical reactions elicited by antigen-antibody interaction does not end with the release of SRS-A and the other mediators (histamine, eosinophil chemotactic factor of anaphylaxis, ECF-A), on the contrary, these mediators especially SRS-A induce the release of prostaglandins of type E (PGE1 and PGE2) which produce bronchodilatation and inhibit the release of SRS-A itself, perhaps being a selfregulating mechanism. The PGF2a, on the other hand, produces bronchoconstriction. The release of SRS-A is also inhibited by the action of diethyl-carbamazine and especially by sodium chromoglicate and compound AH-7725. From the biochemical point of view it is found that the antigen Igells, a serine esterase, initiating several chemical reactions whose consequence is a decrease in the cAMP concentration. This reduction in the cAMP intracellular level is followed by synthesis and excretion of the SRS-A as well as by the aggregation of the microtubules and excretion of the stored histamine. The PGE (1 and 2) acting on one type of membrane receptor and the beta-agonist catecholamines on another produce a common phenomenon: the activation of the adenylcyclase whcih produces the increase of the concentration of cAMP and inhibits the release of mediators of the anapylactic reaction. The parasympathetic system through its chemical mediator acethylcholine, by a mechanism in whcih adenycyclase is not involved is also capable of stimulating the release of histamine and SRS-A. Something similar happens with PGF2a. In conclusion, self-regulatory mechansims for the release of mediators of the anaphylactic reactions may exist. The "perpetuation" of an asthamtic reaction would signify a failure of these self-regulatory mechanisms due to, for example, to a temporary block of the beta-adrenergic receptors, overstimulation of the alfa-receptors or insufficient production of PGE or a transformation of the PGE in PGF.