ED50 Concentration Research Articles

Mechanisms of action of organophosphorus fungicides. I. Kitazin P, inhibitor of phosphatidylcholine biosynthesis in Pyricularia oryzae.

The effect of the organophosphorus fungicide, edifenphos (O-ethyl S, S-diphenyl phosphoro-dithiolate, EDDP, Hinosan®), on DNA, RNA, protein, chitin and lipid biosynthesis was investigated in Pyrieularia oryzae. The incorporation of [2-14C]thymidine, [2-14C]uridine and L-[U-14C]amino acid mixture into DNA, RNA and protein, respectively, was not significantly affected in mycelial cells of P. oryzae treated with 10ppm edifenphos. The fungicide scarcely inhibited chitin synthetase of the microsomal fraction at the ED50 concentration value for mycelial growth. On the other hand, addition of edifenphos to the mycelial cell suspension caused a striking decrease in the incorporation of L-[methyl-14C]methionine and S-adenosyl-L-[methyl-14C]methionine into phospha-tidylcholine, which is the most abundant phospholipid in P. oryzae, but scarcely inhibited the incorporation of [methyl-14C]choline into phosphatidylcholine and that of L-[methyl-14C]methionine into simple lipids. Of enzymes responsible for biosynthesis from glycerol to phosphatidylcholine by way of Greenberg's pathway, phospholipid Nmethyltransferase was specifically inhibited and the ED50 value was 13 ppm. These data suggest that the primary antifungal action of edifenphos is due to interference of phosphatidylcholine biosynthesis by the transmethylation reaction of Sadenosyl-L-methionine. Therefore, the mode of action of edifenphos has a strong resemblance to that of IBP (Kitazin P®).

The inhibitory effects of vasoactive intestinal polypeptide on the mechanical and electrical activity of canine antral smooth muscle.

1. The inhibitory effects of vasoactive intestinal polypeptide (VIP) on the electrical and mechanical activity of canine antral smooth muscle were investigated. 2. In concentrations ranging from 5 X 10(-9) to 1 X 10(-7) M, VIP decreased the force of spontaneous contractions but had no measurable effect on spontaneous action potential complexes. 3. VIP had no effect on the increase in the amplitude and duration of the plateau potential and on the amplitude of contraction caused by a maximally effective concentration of acetylcholine. 4. VIP caused a significant decrease in the force of contraction caused by ED50 and threshold concentrations of acetylcholine. However, VIP had no measurable effect on the increase in the size of the action potential plateau caused by either concentration of acetylcholine. 5. VIP antagonized the increase in the amplitude of the plateau potential and the force of contraction induced by pentagastrin. It had no consistent effect on the pentagastrin-induced increase in frequency. 6. The data indicate that VIP acts as an inhibitor in this tissue in two distinct ways. It uncouples electromechanical coupling during spontaneous and acetylcholine-induced electrical and mechanical activity, and antagonizes pentagastrin-induced increases in electrical and mechanical activities.