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Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine.
J Pharmacol Exp Ther. 1983 Aug; 226(2):519-25.JP

Abstract

Muscarinic receptors, [14C]choline uptake and acetylcholinesterase (AChE) activity in central and peripheral tissues of guinea-pigs treated repeatedly with diisopropylfluorophosphate (DFP) were simultaneously determined. After repeated DFP (1 mg/kg) administration, there was a significant decrease in specific [3H] quinuclidinyl benzilate binding only in the striatum, ileal longitudinal muscle and urinary bladder among various tissues examined. Scatchard analysis revealed that the administration of DFP at 0.5, 1 and 2 mg/kg which depressed the tissue AChE by 50 to 90%, caused a dose-dependent decrease (20-50%) in striatal and ileal [3H]quinuclidinyl benzilate binding sites without a change in the dissociation constant. The lower dose (0.2 mg/kg) of DFP depressed significantly the AChE in both tissues by 30% but failed to alter their [3H]quinuclidinyl benzilate binding sites. High affinity uptake of [14C]choline in the striatum and ileal longitudinal muscle was significantly decreased by repeated administration of DFP at 0.5 and 1 mg/kg but not 0.2 mg/kg. The DFP-induced loss of striatal and ileal muscarinic receptors was effectively antagonized by a concomitant administration of physostigmine (0.5 mg/kg) and atropine (5 mg/kg). Also, these drugs antagonized the DFP-induced decrease in the striatal [14C]choline uptake. Thus, the present study has demonstrated that repeated DFP administration causes a specific decrease in muscarinic receptors and [14C]choline uptake in the striatum and ileal longitudinal muscle of guinea pigs which is closely associated with a considerable (more than 50%) depression of the tissue AChE. In addition, these adaptive changes by DFP were effectively antagonized by physostigmine and atropine.

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Publisher Full Text

Authors

Yamada S
No affiliation info available
Isogai M
No affiliation info available
Okudaira H
No affiliation info available
Hayashi E
No affiliation info available

MeSH

AcetylcholinesteraseAnimalsAtropineCholineCholinesterase InhibitorsCorpus StriatumGuinea PigsIsoflurophateKineticsMaleMusclesPhysostigmineQuinuclidinyl BenzilateReceptors, CholinergicReceptors, MuscarinicUrinary Bladder

Pub Type(s)

Journal Article

Language

eng

PubMed ID

6875862

Citation

Yamada, S, et al. "Correlation Between Cholinesterase Inhibition and Reduction in Muscarinic Receptors and Choline Uptake By Repeated Diisopropylfluorophosphate Administration: Antagonism By Physostigmine and Atropine." The Journal of Pharmacology and Experimental Therapeutics, vol. 226, no. 2, 1983, pp. 519-25.
Yamada S, Isogai M, Okudaira H, et al. Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine. J Pharmacol Exp Ther. 1983;226(2):519-25.
Yamada, S., Isogai, M., Okudaira, H., & Hayashi, E. (1983). Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine. The Journal of Pharmacology and Experimental Therapeutics, 226(2), 519-25.
Yamada S, et al. Correlation Between Cholinesterase Inhibition and Reduction in Muscarinic Receptors and Choline Uptake By Repeated Diisopropylfluorophosphate Administration: Antagonism By Physostigmine and Atropine. J Pharmacol Exp Ther. 1983;226(2):519-25. PubMed PMID: 6875862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlation between cholinesterase inhibition and reduction in muscarinic receptors and choline uptake by repeated diisopropylfluorophosphate administration: antagonism by physostigmine and atropine. AU - Yamada,S, AU - Isogai,M, AU - Okudaira,H, AU - Hayashi,E, PY - 1983/8/1/pubmed PY - 1983/8/1/medline PY - 1983/8/1/entrez SP - 519 EP - 25 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 226 IS - 2 N2 - Muscarinic receptors, [14C]choline uptake and acetylcholinesterase (AChE) activity in central and peripheral tissues of guinea-pigs treated repeatedly with diisopropylfluorophosphate (DFP) were simultaneously determined. After repeated DFP (1 mg/kg) administration, there was a significant decrease in specific [3H] quinuclidinyl benzilate binding only in the striatum, ileal longitudinal muscle and urinary bladder among various tissues examined. Scatchard analysis revealed that the administration of DFP at 0.5, 1 and 2 mg/kg which depressed the tissue AChE by 50 to 90%, caused a dose-dependent decrease (20-50%) in striatal and ileal [3H]quinuclidinyl benzilate binding sites without a change in the dissociation constant. The lower dose (0.2 mg/kg) of DFP depressed significantly the AChE in both tissues by 30% but failed to alter their [3H]quinuclidinyl benzilate binding sites. High affinity uptake of [14C]choline in the striatum and ileal longitudinal muscle was significantly decreased by repeated administration of DFP at 0.5 and 1 mg/kg but not 0.2 mg/kg. The DFP-induced loss of striatal and ileal muscarinic receptors was effectively antagonized by a concomitant administration of physostigmine (0.5 mg/kg) and atropine (5 mg/kg). Also, these drugs antagonized the DFP-induced decrease in the striatal [14C]choline uptake. Thus, the present study has demonstrated that repeated DFP administration causes a specific decrease in muscarinic receptors and [14C]choline uptake in the striatum and ileal longitudinal muscle of guinea pigs which is closely associated with a considerable (more than 50%) depression of the tissue AChE. In addition, these adaptive changes by DFP were effectively antagonized by physostigmine and atropine. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/6875862/Correlation_between_cholinesterase_inhibition_and_reduction_in_muscarinic_receptors_and_choline_uptake_by_repeated_diisopropylfluorophosphate_administration:_antagonism_by_physostigmine_and_atropine_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6875862 DB - PRIME DP - Unbound Medicine ER -