Reserpic acid as an inhibitor of norepinephrine transport into chromaffin vesicle ghosts.

Reserpic acid, a derivative of the antihypertensive drug reserpine, inhibits catecholamine transport into adrenal medullary chromaffin vesicles. Since it does not affect the membrane potential generated by the H+-translocating adenosine triphosphatase but inhibits ATP-dependent norepinephrine uptake with a Ki of about 10 microM, reserpic acid must block the H+/monoamine translocator. Because reserpic acid is much more polar than reserpine, it does not permeate the chromaffin vesicle membrane, nor is it transported into chromaffin vesicle ghosts in the presence of Mg2+-ATP. Although it inhibits norepinephrine transport when added externally, reserpic acid does not inhibit when trapped inside chromaffin vesicle ghosts. Therefore, reserpic acid must bind to the external face of the monoamine translocator and should be a good probe of the translocator's structural asymmetry.