Binding of specific ligands to muscarinic receptors alters the fluidity of membrane fragments from rat brain. A fluorescence polarization study with lipid-specific probes.

The previously suggested method of following ligand-receptor interactions by measuring ligand-induced changes in membrane fluidity [(1986) FEBS Lett. 194, 313-316] was employed to study the binding of specific ligands of the muscarinic receptor to rat brain membrane fragments containing a fluorescent analogue of phosphatidylcholine (APC) as a membrane probe. Upon addition of carbachol and atropine in low concentrations the fluorescence polarization of the APC-labeled membranes decreased significantly demonstrating that binding of these ligands to the muscarinic receptor increases the fluidity of its lipid environment. The fluidity changes were specific, concentration-dependent and saturable. In comparison with radioligand assays the fluorescent lipid probe method proved to be much more sensitive but the Kd values obtained by the two methods differed considerably.