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  • Title: An alteration in sensitivity to cholinergic agents on guinea-pig ilea and atria after repeated administration of an organophosphate and an antagonism by a carbamate.
    Author: Yamada S, Okudaira H, Hayashi E.
    Journal: Arch Int Pharmacodyn Ther; 1979 Sep; 241(1):32-44. PubMed ID: 526070.
    Abstract:
    The effect of 4-methylthiophenyl dipropylphosphate (propaphos, organophosphorus insecticide) and 2-sec-butylphenyl-N-methylcarbamate (BPMC, carbamate insecticide) on the sensitivity to the effects of acetylcholine (ACh), carbachol (CCH) and nicotine was investigated on guinea-pig isolated ilea and atria. The response of these tissues to ACh was significantly enhanced in the presence of propaphos (3.3 x 10(-7) M) or BPMC (4.5 x 10(-6) M), while that to CCH was unaffected. The repeated administration of propaphos (5 mg/kg/day, p.o.) for 7 days had no effect on the contractile responses of guinea-pig ilea to potassium chloride. The responses of ilea and atria to ACh and nicotine were markedly increased by the administration of propaphos, and the values of ED50 and ED80 for their responses were significantly decreased. On the other hand, the response to CCH was decreased as was demonstrated by a significant increase in these values. Pretreatment with BPMC (25 mg/kg/day p.o., 7 days) significantly reduced the alteration in the responsiveness of the tissues to ACh, CCH and nicotine produced by the propaphos administration. The activity of cholinesterase (ChE) declined by 50--70% in blood and tissues from propaphos-treated animals, and its inhibition was significnatly reduced by the pretreatment with PBMC to 30--40%. These results indicate that changes in synaptic ChE activity, as reflected by the changes in ChE activity of blood and tissues, may be responsible for the alteration in sensitivity of ilea and atria to cholinergic agents produced by the repeated administration of propaphos and for the antagonism by BPMC.
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