ARE EXOCYTOSIS MECHANISMS NEUROTRANSMITTER SPECIFIC

Neurotransmission is a multistage regulated process in which a Variety of active molecules contained in vesicles are liberated in response t o specific stimuli from different types of neurone or related cells. T his includes the release of fast neurotransmitters such as amino acids and acetylcholine from central and peripheral synapses, but also that of relatively slow-acting polypeptides from central and peripheral ne urones or neuroendocrine cells. Considerable progress has been made ov er recent years in the understanding at a molecular level of the mecha nism of regulated exocytosis, a crucial phase in this phenomenon. The currently proposed overall mechanism, which incorporates the ''SNARE'' hypothesis for vesicle-membrane docking and fusion, is based on data from experimental models ranging from brain synaptosomes to mast calls . Since the kinetics of the models studied and the physiological effec ts of the neurotransmitters implicated vary so much, it is pertinent t o question whether a general mechanism can be proposed from such exper imental data. This review examines known differences in putative exocy totic mechanisms for the various systems studied and attempts to relat e these to the nature of the active substances released. Differences e xist in each step of the exocytosis process and include the channel th rough which Ca2+ enters to trigger it or the internal Ca2+ source, the type of vesicle in which the transmitter is packaged, the way vesicle s are translocated to the surface membrane or how they dock and fuse w ith it. Major differences have been reported in release mechanisms of different types of vesicle, but minor differences also exist within th e same vesicle class. Thus small synaptic Vesicles and large dense cor e vesicles are translocated by distinct processes and the Ca2+ channel s, Ca2+ sensors and docking proteins involved in other steps are not i dentical in all neuronal phenotypes. It may be concluded that each of these differences has evolved to accommodate the different physiologic al requirements of the neuromodulator released. (C) 1997 Elsevier Scie nce Ltd. All rights reserved.