Prostaglandin, slow-reacting substance, and histamine release from anaphylactic guinea-pig hearts, and its pharmacological modification

Abstract

Prostaglandins (Pgs), slow-reacting substance of anaphylaxis (SRS-A), and histamine were released from anaphylactic isolated perfused guinea pig hearts. Pgs were to the greatest part of the F2alpha-type. PgE2 was found in traces only. Neither PgA2, nor the metabolites 13,14-dihydro-15-keto-PgF2alpha and 13,14-dihydro-15-keto-PgE2 were detected in the perfusates. Isoproterenol reduced the PgF2alpha output significantly. This effect was increased by the addition of theophylline. Propranolol did not reverse the effect of isoproterenol, but in a high concentration (5 mug/ml) reduced the PgF2alpha output for its own. Indomethacin completely abolished the anaphylactic prostaglandin release. The histamine liberation was significantly decreased only by the combination of isoproterenol and theophylline, and also by a high concentration of propranolol (5 mug/ml). In contrast to the Pg release, the anaphylactic SRS-A and histamine liberation was not abolished by indomethacin, but rather increased. The results are discussed in view of the possible role of the released substances in the functional events of cardiac anaphylaxis.

Release of Mediators of Anaphylaxis: Inhibition of Prostaglandin Synthesis and the Modification of Release of Slow Reacting Substance of Anaphylaxis and Histamine

“…When formation of endogenous prostaglandins was inhibited by treatment of passively sensitized human lung with the cyclo-oxygenase inhibitor, indomethacin, an increased amount of SRS-A was released during challenge (Walker, 1972). Similar potentiation of SRS-A release occurred in challenged bovine lungs treated with meclofenamate and aspirin (Burka & Eyre, 1975) and of histamine release from sensitized guinea-pig lungs treated with indomethacin (Gryglewski, Panczenko, Korbut, Grodzinska & Ocetkiewicz, 1975;Liebig, Bernauer & Peskar, 1975). These results suggest that 1 Present address: CIBA-GEIGY AG., Basel, Switzerland.…”

“…When injected or infused into guinea-pig perfused lungs, histamine and SRS-A release rabbit aorta contracting substance (RCS) (a mixture of thromboxane A2 and endoperoxides) and prostaglandin-like material (Palmer et al, 1973;Liebig et al, 1975;Engineer et al, 1976;Engineer et al, unpublished results) so that endoperoxides, thromboxanes, prostacyclin or prostaglandins released in anaphylaxis may influence further release of SRS-A and histamine, perhaps through an interaction with cyclic nucleotides. Further investigation is required to establish the relative importance of individual products of arachidonic acid metabolism.…”

Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis

“…Isolated hearts of ovalbumin-sensitized male guineapigs (350-SSOgbody weight) were perfused and challenged as described previously (Liebig et al, 1975). The hearts were perfused at a constant pressure of 55 cmH2O.…”

“…Bioassay of SRS-A on the guinea-pig isolated ileum treated with mepyramine (3.5 x 10-6M) and atropine (6.9 x 1O-7 M) was performed as described previously (Liebig et al, 1975). Results were expressed in LTD4-equivalents, since the major biological activity of guinea-pig SRS-A is LTD4 (Morris et al, 1980b).…”

“…Release of various mediators like histamine (Schild, 1937;Schild, 1939;Mongar & Schild, 1952;Brocklehurst, 1960;Chakravarty, 1960a;Feigen, Vaughan Williams, Petersen & Nielsen, 1960; Giotti, Guidotti, Mannaioni & Zilletti, 1966;Levi, 1972), slowreacting substance of anaphylaxis (SRS-A) (Brocklehurst, 1960;Chakravarty, 1960b;Liebig, Bemauer & Peskar, 1975), prostaglandin Fu (PGFu,) (Liebig et al, 1975;Levi, Allan & Zavecz, 1976), PGD2 (Anhut, Bernauer & Peskar, 1978), thromboxane B2 (TXB2) (Anhut, Bernauer & Peskar, 1977;Allan & Levi, 1981), the stable degradation product of the vasoconstrictor TXA2 (Moncada & Vane, 1977), and 6-keto-PGF1,, (Peskar, Steffens & Peskar, 1979; Allan & Levi, 1981), the stable degradation product of the vasodilator PGI2 (Moncada & Vane, 1977), in cardiac anaphylaxis has been repeatedly shown. We have previously demonstrated (Anhut et al, 1977) that inhibition of fatty acid cyclo-oxygenase by indomethacin results in inhibition of the initial phase of anaphylactic coronary constriction, but does not prevent the coronary constriction occurring later in the time course of cardiac anaphylaxis.…”