CHARACTERIZATION OF ATP TRANSPORT INTO CHROMAFFIN GRANULE GHOSTS - SYNERGY OF ATP AND SEROTONIN ACCUMULATION IN CHROMAFFIN GRANULE GHOSTS

ATP is an excitatory neurotransmitter that is stored and cosecreted wi th catecholamines from cells of the adrenal medulla, While the transpo rt of catecholamines into chromaffin granule ghosts has been extensive ly characterized, there is little information on the mechanism of ATP transport into these structures, Here Fee show that ATP transport is d riven by the electrical component of the electrochemical proton gradie nt created by the chromaffin granule membrane H+-ATPase, and that the accumulated nucleotide is released from the vesicles by inhibition of the H+-ATPase, GTP and UTP are also substrates for this transporter, d istinguishing it from the mitochondrial ADP/ATP exchanger, Accumulatio n of ADP and ATP (rather than exchange with intravesicular ATP) is dem onstrated by high pressure liquid chromatography measurements, The ani on transport inhibitor 4,4-diisothiocyanatostilbene-2,2-disulfonic aci d (K-i = 27 mu M) inhibits ATP transport, while atractyloside, the inh ibitor of the mitochondrial ATP/ADP exchanger, is a very poor inhibito r, Finally, we have demonstrated a synergy between the accumulation of ATP and that of serotonin (i.e. more of each solute accumulates when the two are accumulated together), supporting the view that there is a n interaction between serotonin and ATP that reduces their effective c oncentration within the ghosts.