@article {Stokke1366, author = {M Stokke and E M Hagelin and C Poulsson and R Patel and Y Haile and O Br{\o}rs}, title = {Inhibition by amiloride and quinacrine of specific [3H]nitrendipine binding to rat cardiac membranes.}, volume = {260}, number = {3}, pages = {1366--1372}, year = {1992}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Binding studies were designed to test if and how amiloride and quinacrine affected the specific binding of [3H]nitrendipine (NIT) to rat cardiac membranes. Specific binding of NIT was inhibited in a dose-dependent manner by amiloride [Hill coefficient (nH), 1.46; concentration of inhibitor producing 50\% inhibition (K0.5) = 9.2 x 10(-4) M] and quinacrine (nH = 0.54, K0.5 = 7.7 x 10(-6) M). The inhibitions were incomplete in the presence of 10(-3) M Ca ions. The Hofstee plot was convex upwards for amiloride and concave upwards for quinacrine. Amiloride increased the Kd, decreased the maximum specific binding and increased the k-1. Quinacrine increased the Kd without changing the maximum specific binding and increased the k-1. The effects of amiloride and quinacrine on k-1 were nonadditive. We conclude that amiloride and quinacrine bind to or close to the L-type Ca channel, and inhibit the specific binding of NIT by allosteric, complex interactions influenced by the free concentration of Ca++. The nonadditive allosteric effects suggest a shared mechanism of interaction for amiloride and quinacrine with the site(s) of NIT. Several mechanisms are discussed to explain how amiloride and quinacrine can produce such inhibition of NIT binding.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/260/3/1366}, eprint = {https://jpet.aspetjournals.org/content/260/3/1366.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }