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Molecular Pharmacology, Vol 8, 222-229, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

The Role of Calcium Ions in the Interaction of Amiloride with Membrane Receptors

A. W. CUTHBERT 1 and P. Y. D. WONG 1

1 Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom

When amiloride is added to the solution bathing the external surface of frog skin there is an immediate and reversible inhibition of the short-circuit current. However, if the external surface is bathed in calcium-free solutions containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA), the inhibitory effects of amiloride are severely reduced or abolished. If calcium is readmitted to the external solution, the inhibitory effects of amiloride are restored. Other ions (Mg2+, Sr2+, La3+, and Mn2+) can substitute for calcium in these interactions. Quantitative considerations suggest that amiloride may form a ternary complex with Ca2+ and a membrane receptor controlling the access of sodium to the transport mechanism.

Note:
ACKNOWLEDGMENT We are grateful to Merck Sharp & Dohme for a gift of amiloride.

Submitted on November 9, 1971






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