Open AccessRole of a transmembrane pH gradient in epinephrine transport by chromaffin granule membrane vesicles.
Author(s) -
Shimon Schuldiner,
Hanna Fishkes,
Baruch I. Kanner
Publication year - 1978
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.75.8.3713
Subject(s) - electrochemical gradient , nigericin , valinomycin , chemistry , adrenal medulla , chromaffin cell , epinephrine , vesicle , biophysics , antiporter , reserpine , atpase , granule (geology) , biochemistry , proton transport , membrane potential , membrane , catecholamine , biology , endocrinology , paleontology , enzyme
ATP-driven transport and accumulation of epinephrine in chromaffin granule membrane vesicles isolated from bovine adrenal medulla is inhibited by the proton ionophores carbonylcyanide p-trifluoromethoxyphenylhydrazone and nigericin, but not by valinomycin. Moreover, an artificially imposed pH gradient (interior acid) is able to drive this reserpine-sensitive transport system in the absence of ATP. Dicyclohexylcarbodiimide, an inactivator of the chromaffin granule membrane-bound ATPase, completely inhibits ATP-dependent epinephrine accumulation, but has much less effect when an imposed pH gradient is the driving force for epinephrine transport. The findings provide a strong indication that a pH gradient (interior acid) is the immediate driving force for epinephrine uptake in these storage granules and suggest that ATP-driven epinephrine transport is the result of two processes: (i) generation of a proton electrochemical gradient (interior acid and positive) by the membrane-bound, proton-translocating ATPase; and (ii) pH gradient-driven accumulation of the catecholamine.