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The catecholamine carrier of bovine chromaffin granules. Form of the bound amine

D Scherman and JP Henry

The binding of [2-3H]dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10- dimethoxy-1,2,3,-4,6,7-hexahydro-11bH-benzo [a]quinolizine), a tetrabenazine derivative which binds to the catecholamine carrier of chromaffin granule membranes, has been studied as a function of the pH. The number of binding sites was constant from pH 6.5 to pH 9.0, whereas the KD decreased to a minimal plateau value, obtained at pH values higher than 7.5, the drug pKa. The pH dependency of the displacement of [3H]dihydrotetrabenazine by noradrenaline was also investigated. Noradrenaline KD values derived from displacement experiments decreased logarithmically when the pH increased from 6.5 to 8.5, i.e., for pH values lower than the pKa of noradrenaline. These pharmacological data support our previous hypothesis based on kinetic data [Scherman and Henry, Eur. J. Biochem. 116:535-539 (1981)] that the monoamine carrier of the chromaffin granule membrane binds and transports neutral amines, a form of low abundancy at physiological pH but for which it has a high affinity.

Volume 23, Issue 2, pp. 431-436, 03/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics