Effect of drugs on the ATP-induced and pH-gradient-driven monoamine transport by bovine chromaffin granules

Abstract

Reserpine, tetrabenazine and the neuroleptics chlorpromazine and haloperidol blocked the ATP-dependent uptake of noradrenaline and tyramine by ghosts derived from bovine chromaffin granules. The drugs did not affect chromaffin granules energization since they were without any effect on the membrane ATPase activity and on the transmembrane potential and pH-gradient generated by the ATP-dependent H +-translocase. Differences were observed in the inhibitory effect of the drugs on the monoamine uptake by ghosts acidic with respect to the external medium. These differences were accounted for by the existence under these conditions of two mechanisms of uptake, as shown by kinetic experiments. Noradrenaline was taken up by a carrier-mediated process which was blocked by all drugs, whereas tyramine transport involved non-specific diffusion of its unprotonated form, a process which was sensitive to neuroleptics and high doses of reserpine. From the kinetic and pharmacological studies of tyramine uptake, it is concluded that the ATP-dependent active transport of monoamines requires a carrier-mediated process even for amines which are rapidly transported by non-specific diffusion through the membrane.