Ligand interactions with membrane-bound porcine atrial muscarinic receptor(s)
- 9 December 1980
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 19 (15), 3407-3413
- https://doi.org/10.1021/bi00556a001
Abstract
Ligand interactions with the membrane-bound muscarinic acetylcholine receptor in porcine atria are characterized by using [3H]quinuclidinyl benzilate [[3H]QNB] as a probe for the receptor. Antagonists and local anesthetics appear to displace QNB from a single population of high-affinity sites while agonists appear to interact with 2 noninterconvertible subpopulations of QNB binding sites. The simplest mechanism that appeared to be consistent with both kinetic and thermodynamic studies of [3H]QNB binding to the receptor required 2 steps. The first step, in rapid preequilibrium (K = 1.8 .times. 10-9 M), was followed by a slow ligand-induced conformational change (k1 = 5.5 .times. 10-3 s-1; k-1 = 3.3 .times. 10-4 s-1) of the receptor-QNB complex. The overall dissociation constant calculated from the kinetic data (1.09 .times. 10-10 M) was in good agreement with that determined from equilibrium measurements (KOV = 1.22 .times. 10-10 M). The complex behavior of the dissociation rate constant for [3H]QNB in the presence of competing ligands may indicate that at high concentrations these ligands either bind to a second low-affinity site(s) on the protein, altering the properties of the high-affinity site, or they nonspecifically alter the properties of the membrane, creating a 2nd population of QNB-receptor complexes that dissociate with an observed rate constant equal to .apprx. 3 .times. 10-5 s-1.This publication has 1 reference indexed in Scilit:
- BIOCHEMICAL STUDIES ON MUSCARINIC ACETYLCHOLINE RECEPTORSJournal of Neurochemistry, 1976