No abstract

Rabbits were imn~unized with a conjugate of leukotriene (LT) C4 and bovine serum albumin prepared by coupling the single free amino group of the hapten to the protein using gluteraldehyde. Binding of [3H]LTC4 to the antibodies obtained is inhibited by 50% with 1.5 ng LTC4. The relative cross-reaction of LTD 4 is 16% and of LTC4-methyl ester 3.6%. The validity of the radioimmunoassay was demonstrated by comparison with bioassay using the isolated guinea pig ileum. Using the radioimmunoassay it could be shown that endogenous LTC4 is released in a dose-dependent manner by human polymorphonuclear leucocytes stimulated with the divalent cation ionophore A23187. Leukotriene C4 Radioimmunoassay Leucocyte Bioassay LipoxygenaseSlow-reacting substance

1 The effects of infusions of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 1.1 x 10-molmin-') and the antagonist of slow-reacting substance of anaphylaxis (SRS-A) FPL 55712 (1.2 x 10-mol min-') on the coronary constriction and the release of SRS-A, leukotriene C4-like immunoreactivity, thromboxane B2 and 6-keto-prostaglandin Fl. from perfused anaphylactic guinea-pig hearts were investigated. 2 Both NDGA and FPL 55712 in the concentrations used induced an increase in basal coronary flow, but did not prevent the coronary flow reduction in the early phase (0-4 min) after antigen injection. On the other hand, NDGA and FPL 55712 inhibited the less pronounced long-lasting coronary flow reduction in the later phase of cardiac anaphylaxis. 3 NDGA decreased the release of SRS-A from the anaphylactic guinea-pig hearts below or close to the detection limit of the bioassay and simultaneously diminished the release of leukotriene C4-like immunoreactivity. On the other hand, FPL 55712 did not influence the amounts of leukotriene C4-like immunoreactivity released in cardiac anaphylaxis. 4 Neither NDGA nor FPL 55712 affected the release of immunoreactive thromboxane B2 (TXB2) from anaphylactic guinea-pig hearts. Release of 6-keto-prostaglandin Flm after challenge, however, was decreased by NDGA, while FPL 55712 had no significant effect. 5 These results suggest, that SRS-A may be a relatively more important mediator in the late phase of coronary constriction occurring during cardiac anaphylaxis, while the effects of other mediators, particularly vasoconstrictor cyclo-oxygenase products, seem to prevail in the early phase.

Na-alginate as well as guar gum inhibit the absorption of a ⁵⁹Fe-labelled iron dose (360 nmol) from tied-off jejunal segments of either normal or iron-deficient rats. In order to inhibit the absorption of the iron dose by half as compared with normal rats to which ionized iron was administered 1.2–8 mg of guar gum and 8–30 mg Na-alginate was necessary. In iron-deficient rats the highest dose of Na-alginate tested, 100 mg, inhibited the absorption of iron by about 20%; the highest dose of guar gum, 30 mg, inhibited the amount of iron absorbed by about 25%. An artificial diet containing 10% of either guar gum and Na-alginate fed for 3 days inhibited the absorption of iron in normal but not in iron-deficient rats. Also, in these experiments guar gum proved to be more effective than Na-alginate.

Anthralin is an inhibitor of oxidative phosphorylation at concentrations found in vivo. ADP-stimulated oxygen consumption is diminished. Consequently, the rate of ATP synthesis is reduced and mitochondrial ATP content declines. Neither the isolated ATPase (F1F0-ATPase), nor the mitochondrial membrane-bound ATPase are influenced by the drug. Respiration under resting conditions is not affected. The experimental data unequivocally indicate that anthralin is not an uncoupler of oxidative phosphorylation, as previously stated. Furthermore, the interpretation that respiratory deficiency induced in yeast strains by anthralin is a consequence of petite mutations has to be reconsidered. Under in vivo conditions, anthralin inhibits respiration per se. Our experiments, including the electron spin resonance spectroscopy, reveal that anthralin alters mitochondrial membrane structure and function simultaneously. A redox or free-radical mediated step may be involved. In consequence, inhibition of ATP production occurs which may become the limiting factor for increased cellular metabolism in psoriasis.