The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors
Abstract
The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(2-(-(8-dipropylamino)methyl)-1-piperidinyl-ethyl-amino-carbonyl)-6H-pyrido (2,3-b) (1,4)benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of (3H)AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that (3H)AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.
- Authors:
-
- Department of Biochemical Research, Dr. Karl Thomae GmbH Biberach (West Germany)
- Publication Date:
- OSTI Identifier:
- 5080357
- Resource Type:
- Journal Article
- Journal Name:
- Journal of Receptor Research; (United States)
- Additional Journal Information:
- Journal Volume: 11:1-4; Journal ID: ISSN 0197-5110
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; PARASYMPATHOLYTICS; BIOCHEMICAL REACTION KINETICS; SYMPATHOMIMETICS; RECEPTORS; CPB; MUSCLES; RATS; SMALL INTESTINE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; DIGESTIVE SYSTEM; DRUGS; GASTROINTESTINAL TRACT; HYDROGEN COMPOUNDS; INTESTINES; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; MEMBRANE PROTEINS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; REACTION KINETICS; RODENTS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques
Citation Formats
Entzeroth, M, and Mayer, N. The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors. United States: N. p., 1991.
Web. doi:10.3109/10799899109066395.
Entzeroth, M, & Mayer, N. The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors. United States. https://doi.org/10.3109/10799899109066395
Entzeroth, M, and Mayer, N. 1991.
"The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors". United States. https://doi.org/10.3109/10799899109066395.
@article{osti_5080357,
title = {The binding of (3H)AF-DX 384 to rat ileal smooth muscle muscarinic receptors},
author = {Entzeroth, M and Mayer, N},
abstractNote = {The tritiated cardioselective muscarinic antagonist AF-DX 384 (5,11-dihydro-11-(2-(-(8-dipropylamino)methyl)-1-piperidinyl-ethyl-amino-carbonyl)-6H-pyrido (2,3-b) (1,4)benzodiazepin-6-one) was used to label muscarinic receptors in the rat ileum. Saturation binding to membrane suspensions revealed a high affinity binding site with a Kd of 9.2 nM. The maximal number of binding sites labeled in this tissue (Bmax) is 237 fmol/mg protein. The association and dissociation kinetics were well represented by single exponential reactions, and the dissociation constant obtained from the ratio of rate constants was in agreement with that derived from saturation experiments. Specific binding was inhibited by muscarinic antagonists with a rank order of potencies of atropine (pKi: 8.80) greater than 4-DAMP (pKi: 8.23) = AF-DX 384 (pKi: 8.20) greater than AF-DX 116 (pKi: 7.09) = hexahydro-sila-difenidol (pKi: 6.97) greater than pirenzepine (pKi: 6.49) and is consistent with the interaction of (3H)AF-DX 384 with muscarinic receptors of the M2 subtype. It can be concluded that (3H)AF-DX 384 can be used to selectively label M2 muscarinic receptors in heterogeneous receptor populations.},
doi = {10.3109/10799899109066395},
url = {https://www.osti.gov/biblio/5080357},
journal = {Journal of Receptor Research; (United States)},
issn = {0197-5110},
number = ,
volume = 11:1-4,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 1991},
month = {Tue Jan 01 00:00:00 EST 1991}
}