TY - JOUR
T1 - Method for comparing selectivities of unlabeled subpopulation-selective ligands
T2 - Application to muscarinic receptors
AU - Ellis, John
N1 - Funding Information:
ACKNOWLEDGEMENTS The excellent technical assistance of Margaret Seidenberg is gratefully acknowledged. Supported by PHS grants ROlAG05214 and R2320740 and by a grant from the Vermont Chapter of the American Heart Association.
PY - 1988
Y1 - 1988
N2 - A method for comparing the selectivities of two unlabeled ligands by simultaneous competition for the binding of a nonselective labeled ligand has been illustrated by computer simulations. Experimental application of this approach indicated that the subpopulations of muscarinic receptors that are distinguished by the use of quaternary antagonists are not related to the M1 and M2 subtypes (based on pirenzepine). However, the quaternary agonist carbachol was found to express both modes of selectivity. The method should be particularly useful in the evaluation of new ligands when labeled selective ligands are unavailable. Further, this method complements experiments that can be carried out with a labeled selective ligand, since it emphasizes the contribution of the sites for which the selective ligand has low affinity.
AB - A method for comparing the selectivities of two unlabeled ligands by simultaneous competition for the binding of a nonselective labeled ligand has been illustrated by computer simulations. Experimental application of this approach indicated that the subpopulations of muscarinic receptors that are distinguished by the use of quaternary antagonists are not related to the M1 and M2 subtypes (based on pirenzepine). However, the quaternary agonist carbachol was found to express both modes of selectivity. The method should be particularly useful in the evaluation of new ligands when labeled selective ligands are unavailable. Further, this method complements experiments that can be carried out with a labeled selective ligand, since it emphasizes the contribution of the sites for which the selective ligand has low affinity.
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U2 - 10.3109/10799898809049032
DO - 10.3109/10799898809049032
M3 - Article
C2 - 3193406
AN - SCOPUS:0023693565
SN - 1079-9893
VL - 8
SP - 885
EP - 900
JO - Journal of Receptors and Signal Transduction
JF - Journal of Receptors and Signal Transduction
IS - 6
ER -