Anti-B-50 (GAP-43) antibodies decrease exocytosis of glutamate in permeated synaptosomes

The involvement of the protein kinase C substrate, B-50 (GAP-43), in the re lease of glutamate from small clear-cored vesicles in streptolysin-O-permea ted synaptosomes was studied by using anti-B-50 antibodies. Glutamate relea se was induced from endogenous as well as H-3-labelled pools in a [Ca2+]-de pendent manner. This Ca2+-induced release was partially ATP dependent and b locked by the light-chain fragment of tetanus toxin, demonstrating its vesi cular nature. Comparison of the effects of anti-B-50 antibodies on glutamat e and noradrenaline release from permeated synaptosomes revealed two major differences. Firstly, Ca2+-induced glutamate release was decreased only par tially by anti-B-50 antibodies, whereas Ca2+-induced noradrenaline release was inhibited almost completely. Secondly, anti-B-50 antibodies significant ly reduced basal glutamate release, but did not affect basal noradrenaline release. In view of the differences in exocytotic mechanisms of small clear -cored vesicles and large dense-cored vesicles, these data indicate that B- 50 is important in the regulation of exocytosis of both types of neurotrans mitters, probably at stages of vesicle recycling and/or vesicle recruitment , rather than in the Ca2+-induced fusion step. (C) 1998 Elsevier Science B. V. All rights reserved.