Molecular Pharmacology, Vol 14, 138-144, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Interaction of Dibucaine and Calcium Ion on a Calcium Pump Reconstituted from Defined Components of Intestinal Brush Border

¹ Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108, Japan

The uptake of Ca⁺⁺ by reconstituted proteoliposomes involves an ATP-independent as well as an ATP-dependent process. In the presence of 0.7 mM ATP, 1 mM dibucaine inhibited Ca⁺⁺ uptake and (Mg⁺⁺ + Ca⁺⁺)-ATPase activity, but 0.2 mM dibucaine stimulated both. The latter reduced the velocity of ATP-independent Ca⁺⁺ uptake at low Ca⁺⁺ concentrations, but increased it at a high concentration (0.15 mM of Ca⁺⁺. ATP-dependent Ca⁺⁺ uptake was facilitated by 0.2 mM dibucaine only in the presence of a high concentration of Ca⁺⁺. Kinetic analyses of the data obtained with the lower dose of dibucaine suggest that this compound competes with Ca⁺⁺ for binding sites on the outer surface of membranes and that its interaction with Ca⁺⁺ induces a conformational change of membranes accompanied by an increase in the passive permeability of Ca⁺⁺ and activation of the ATP-mediated Ca⁺⁺ pump.