Tolerance following organophophate poisoning of tracheal muscle. Annual report
The effects of subacute exposure to the organophosphate acetylcholinesterase inhibitors (diisoprophylfluorophosphate, soman, sarin, and VX) on the binding properties of muscarinic receptors, the contractile responses, and the electrophysiological properties of swine tracheal smooth muscle were studied. Subacute organophosphate treatment decreased the number of muscarinic receptors in smooth muscle homogenates and in the surface membrane of isolated cells by 50-77%. DFP was the most potent, followed by sarin, VX, and soman. The organophosphates induced a change in the coupling of the receptor to the guanine nucleotide-binding protein, which resulted in a decrease in the number of high-affinity receptors available for agonist-induced actions. The sensitivity of the muscle to acetylcholine and bethanechol was largely unchanged by any of the organophosphates. It is concluded that tolerance development is a complex process and involves: changes in receptor number and coupling of these receptors to intra-cellular processes; changes in the sensitivity of the ganglia to cholinergic agonists; and changes in the membrane processes and channels controlling membrane potential. Surprisingly, the response of the muscle to agonists is not greatly affected even though 70% of the receptors are lost from the cell surface.
- Research Organization:
- Mississippi Univ., Jackson (USA). Medical Center
- OSTI ID:
- 6648729
- Report Number(s):
- AD-A-198498/8/XAB
- Country of Publication:
- United States
- Language:
- English
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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
BIOLOGICAL ADAPTATION
BIOLOGICAL EFFECTS
BODY
CHEMICAL BONDS
CHEMICAL WARFARE AGENTS
CONTRACTION
DOCUMENT TYPES
DOMESTIC ANIMALS
DRUGS
ELECTROPHYSIOLOGY
ESTERS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
MAMMALS
MUSCLES
NEUROREGULATORS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PHYSIOLOGY
PROGRESS REPORT
PURINES
QUATERNARY COMPOUNDS
RESPIRATORY SYSTEM
SENSE ORGANS
SENSITIVITY
SURFACES
SWINE
TOLERANCE
TRACHEA
VERTEBRATES
WEAPONS