This laboratory has studied the storage of norepinephrine (NE) in synaptic vesicles in the axoplasm within adrenergic nerve terminals (in situ). Storage depended upon energy utilizing reactions involving ATP at the membranes of vesicles (Bogdanski and Blaszkowski, 1973). The results of other studies have shown that vesicles in situ respond to known inhibitors of the uptake dependent upon Mg++ -ATPase activity in the membranes of isolated vesicles (Bogdanski, 1982; 1983; 1986; 1988). In isolated vesicles, the activity of MS++ -ATPase drives protein transport to generate electrochemical gradients of protons across the vesicle membrane. These gradients drive the transport of NE. Biochemical reagents which block or dissipate the gradients of H+ block uptake and, generally, release NE from vesicles in situ. The past years' work has dealt primarily with the inhibitory effect of ammonia on storage by vesicles in situ. This alkalinizing reagent for vesicles blocks ATP-dependent uptake, and releases NE from vesicles. A series of such responses were compared with those of reserpine, which blocks uptake and releases NE but has no effect on electrochemical gradients of H+.
