title: 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-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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National University of Singapore, 19260, Singapore, Singapore.
authors.forename: S L
authors.initials: SL
authors.lastname: Lim
authors.forename: M K
authors.initials: MK
authors.lastname: Sim
authors.forename: W K
authors.initials: WK
authors.lastname: Loke
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D000110:Acetylcholinesterase; D010646:Phentolamine