RT Journal Article SR Electronic T1 The Role of Calcium Ions in the Interaction of Amiloride with Membrane Receptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 222 OP 229 VO 8 IS 2 A1 A. W. CUTHBERT A1 P. Y. D. WONG YR 1972 UL http://molpharm.aspetjournals.org/content/8/2/222.abstract AB 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(β-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. ACKNOWLEDGMENT We are grateful to Merck Sharp & Dohme for a gift of amiloride.