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Two opposite dose-dependent effects of diazinon on the motor activity of the rat ileum

Trailović, Saša M., Marjanović, Djordje S., Uzelac, Teodora Vidonja, Milovanović, Mirjana, Trailović, Jelena Nedeljković
Research in veterinary science 2017 v.112 pp. 18-25
Ascaris suum, cholinergic receptors, diazinon, dose response, ileum, invertebrates, median effective concentration, poisoning, rats, washing
Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly. In the same preparation, diazinon 3nM, significantly increased contractions induced by EFS, but did not affect the contractions caused by 5MFI. Contrarily, 1μM of diazinon significantly and reversibly inhibited the EFS-induced ileal contractions. Diazinon exhibited competitive and non-competitive inhibitions of 5MFI induced contractions. The control EC50 of 5MFI was 2.48μM with Rmax=1.88g. In the presence of diazinon, EC50 was 12.45μM, while Rmax was reduced to 0.43g. After washing, the EC50 and Rmax values were again closer to the control level (3.80μM and 1.04g). Diazinon 1μM did not inhibit Ascaris suum contractions caused by ACh, but it increased the Rmax. Diazinon in our study exhibits two opposite effects on the motor activity of the ileum. In low nanomolar concentrations the dominat is its effect on AChE and the stimulation of contractions. Furthermore, in concentrations that approach micromolar values diazinon has a direct inhibitory effect on muscarinic receptors. The direct inhibitory effect of diazinon on A. suum contractions was not found.