Acetylcholinesterase-independent action of diisopropyl-flurophosphate in the rat aorta

Eur J Pharmacol. 2000 Sep 22;404(3):353-9. doi: 10.1016/s0014-2999(00)00629-4.

Abstract

Recent studies have shown that many organophosphates can bind competitively and noncompetitively to membrane muscarinic receptors. The present study investigated the responses of the rat aortic rings to diisopropyl-flurophosphate (DFP), an organophsophorus cholinesterase inhibitor, and the possible involvement of muscarinic receptors. DFP caused a concentration-dependent contraction when added cumulatively from 10(-8) to 10(-4) M. This contraction was inhibited in a noncompetitive manner by high concentrations of atropine (1.5 x 10(-6) and 1.8 x 10(-6) M) but was unaffected by similar concentrations of selective muscarinic receptor subtype antagonists, pirenzepine, 11-2[2-[(diethylamino)methyl]-1-piperidinyl]acetyl-5, 11-dihydro-6H-rido[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) and 4-Diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP). Phentolamine, an alpha-adrenoceptor antagonist, was able to inhibit the DFP-induced contraction in a noncompetitive manner at a concentration of 10(-7) M. These findings suggested that the DFP-induced contraction in the rat aortic rings was mediated by norepinephrine that was released from sympathetic nerve terminals present in the aortic rings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aorta / drug effects*
  • Aorta / physiology
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Isoflurophate / pharmacology*
  • Male
  • Phentolamine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Vasoconstriction / drug effects*
  • Vasoconstriction / physiology

Substances

  • Adrenergic alpha-Antagonists
  • Cholinesterase Inhibitors
  • Isoflurophate
  • Acetylcholinesterase
  • Phentolamine