Binding of hydrophobic drugs to lipid bilayers and to the (Ca2+ + Mg2+)-ATPase.
Microelectrophoretic studies of the binding of a number of commonly used hydrophobic amine drugs to liposomes demonstrated the existence of relatively large surface potentials associated with binding of the protonated forms of the drugs. A theoretical treatment based on Langmuir adsorption isotherms and the Gouy-Chapman theory of the diffuse double layer allows estimation of drug-binding constants from electrophoretic mobility data. Such constants allow calculation of the charge effects arising from drug binding in more complex membrane systems, and it is shown that shifts in the apparent Ca+ affinity of the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum in the presence of hydrophobic amine drugs are readily explicable in terms of the electrostatic effects of drug binding.
D000588:Amines / Q000494:pharmacology; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008051:Lipid Bilayers; D008433:Mathematics; D008564:Membrane Potentials; D009132:Muscles / Q000201:enzymology; D010600:Pharmacology; D010713:Phosphatidylcholines; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013696:Temperature
D000588:Amines; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases