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

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-6 H-rido[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) and 4-Diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP). Phentolamine, an α-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. (C) 2000 Elsevier Science B.V.