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Molecular Pharmacology, Vol 9, 571-579, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

The Cooperativity of ggr-Aminobutyric Acid Action on the Membrane of Locust Muscle Fibers

NEVILLE BROOKES 1 and ROBERT WERMAN 2

1 Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
2 Institute of Life Sciences, Hebrew University, Jerusalem, Israel

Dose-response curves of the action of ggr-aminobutyric acid to increase the conductance of postsynaptic membrane were measured in fibers of the flexor tibialis muscle of the metathoracic leg of Locusta migratoria. The sigmoid shape of the curves is interpreted in terms of the cooperative binding of more than 1 ggr-aminobutyric acid molecule to the receptor. The "function of state," which describes the particular case in which receptor activation is induced only after the binding of more than 1 ligand molecule, is compared with some other formulations of cooperative binding, and is shown to give a better fit to the experimental data. This function uniquely predicts that the limiting Hill slope at small concentrations equals n, the number of molecules required to activate a receptor. In the present experiments n appears to be 3.

Submitted on December 8, 1972




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