Effect of propylbenzilylcholine mustard on contraction and radioligand binding parameters of muscarinic receptors in guinea pig ileum
The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate binding sites respectively to be compared with a 62% and a 85% decrease expected from calculated q-values. K/sub A/-values for the methyl and ethyl derivative agreed well with the dissociation constants for the high affinity agonist sites determined from displacement of (/sup 3/H-)-1-Quinuclidinyl benzilate. The K/sub A/-value for the propylfurtrethonium corresponds to the low affinity agonist dissociation constant. The fraction of receptors in the high affinity agonist state differs considerably for the three furtrethonium derivatives investigated. Neither the fraction of receptors in the high affinity agonist state, nor the ratio of dissociation constants for these states is affected by the alkylation of 85% of the functional muscarinic receptors. The inactivation of components of the effector system by PrBCM seems unlikely. 22 references, 3 figures, 3 tables.
- Research Organization:
- Univ. of Nijmegen, Netherlands
- OSTI ID:
- 6076119
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 41:17; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
BENZILIC ACID
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACIDS
CHOLINE
CONTRACTION
DATA
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EXPERIMENTAL DATA
GASTROINTESTINAL TRACT
GUINEA PIGS
HYDROXY ACIDS
HYDROXY COMPOUNDS
INFORMATION
INTESTINES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MUSCLES
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
RECEPTORS
RESPONSE MODIFYING FACTORS
RODENTS
SMALL INTESTINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES