PT - JOURNAL ARTICLE AU - Hadley L. Conn, Jr. AU - Robert J. Luchi TI - IONIC INFLUENCES ON QUINIDINE-ALBUMIN INTERACTION DP - 1961 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 76--83 VI - 133 IP - 1 4099 - http://jpet.aspetjournals.org/content/133/1/76.short 4100 - http://jpet.aspetjournals.org/content/133/1/76.full SO - J Pharmacol Exp Ther1961 Jul 01; 133 AB - In vitro studies were made of the effects on quinidine-albumin binding of varying concentrations of hydrogen, calcium, chloride, sodium and potassium ions. Concentrations of the first three ions, beyond the physiological range, markedly reduced quinidine-albumin binding. Under concentration conditions obtainable in living organisms lesser effects of the first two ions and minimal effects of chloride ion were demonstrated. No effects on quinidine-albumin interaction were attributable to the presence of sodium or potassium ions in concentrations as great as or greater than those occurring in the body. The characteristics of the relationship between pH and the fraction of quinidine bound by albumin conform to the view that an imidazole group in histidine represents one site in the albumin molecule interacting with the quinidine molecule. The chloride inhibition of binding possibly reflects the involvement of a second interaction site in the albumin molecule, a tyrosine or serine residue. Translation of the present data to ionic influences on serum binding of quinidine by albumin seems reasonable. Whether, however, ion induced alterations in serum binding of quinidine can directly affect drug action is not demonstrated and seems doubtful. The possibility is raised that these presumed ion induced changes in serum binding of quinidine may reflect similar changes in binding of quinidine by certain of the cell proteins. If this speculation is correct changes in the intracellular ionic milieu, particularly changes in H+ and Ca++, may have an important bearing on quinidine binding in cells, on quinidine action, and on quinidine toxicity.