Changes in biochemical properties of muscarinic receptors in diisopropylfluorophosphate (DFP)-treated swine

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6936524

Farley, J M; Yang, C M; Mohan, P M; Dwyer, T M

Daily administration of DFP produced 90-95% inhibition of cholinesterase in homogenates of striatum and tracheal smooth muscle. Scatchard analysis of saturation isotherms revealed a decrease in the maximal density of receptor from 1.7 to 0.8 pmole/mg protein in striatum and from 1.8 to 0.4 pmole/mg protein in tracheal smooth muscle as compared with controls. This decrease in quinuclidinyl benzilate ((/sup 3/H)QNB) binding was not due to a direct effect of DFP on muscarinic receptors since no inhibition of binding was produced by high concentration of DFP when added in vitro or by short-term treatment in vivo. There was no significant change in the affinity of receptors (K/sub D/). The Ki values for inhibition of (/sup 3/H)QNB binding by various cholinergic drugs were determined. Analysis of carbachol inhibition of (/sup 3/H)QNB binding using a two binding site model in control demonstrated the existence of low (KI1 = 1.2 x 10/sup -4/ M) and high (KI2 = 1.7 x 10/sup -7/ M) affinity binding sites with relative densities of 45.7 and 54.3%, respectively. Daily treatment with DFP for 7 days resulted in a KI1 of 2.2 x 10/sup -5/ M and a KI2 of 1.8 x 10/sup -7/ M with relative densities of 66.7 and 33.3%, respectively. These findings suggested that subacute administration of DFP caused not only a down-regulation of muscarinic receptors but also an interconversion of high to low affinity states.

• Research Organization: Univ. of Mississippi Medical Center, Jackson
• OSTI ID: 6936524
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BENZILIC ACID
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CHEMICAL PROPERTIES
CHOLINE
CHOLINESTERASE
DOMESTIC ANIMALS
DRUGS
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
HYDROLASES
HYDROXY ACIDS
HYDROXY COMPOUNDS
ISOTHERMS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MUSCLES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHORIC ACID ESTERS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
RECEPTORS
SWINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES