A GAMMA-AMINOBUTYRIC-ACID TRANSPORTER DRIVEN BY A PROTON PUMP IS PRESENT IN SYNAPTIC-LIKE MICROVESICLES OF PANCREATIC BETA-CELLS

A variety of peptide-secreting endocrine cells contain a population of recycling microvesicles that share several major membrane polypeptide s with neuronal synaptic vesicles (SVs). The function of these synapti c-like microvesicles (SLMVs) remains to be elucidated. It was previous ly suggested that SLMVs of pancreatic beta cells may store and secrete gamma-aminobutyric acid (GABA). GABA, the major nonpeptide inhibitory neurotransmitter of the central nervous system, is stored in and secr eted from SVs. GABA uptake into SVs is mediated by a transporter that is driven by a vacuolar proton ATPase. GABA is also present at high co ncentration in the endocrine pancreas where it is selectively localize d in insulin-secreting beta cells, the core cells of pancreatic islets . GABA is not present in peripheral islet cells (mantle cells), repres ented primarily by glucagon-secreting alpha cells. In this study, an i mmunoisolation procedure was used to purify SLMVs from cell lines deri ved from mouse beta cells and alpha cells. SLMVs obtained from the bet a-cell line, but not those obtained from the alpha-cell line, displaye d a GABA-transport activity dependent upon a proton electrochemical gr adient generated by a vacuolar proton ATPase. These data support the h ypotheses that (i) SLMVs have a secretory function similar to that of SVs and (ii) beta-cell SLMVs are involved in the secretion of GABA, wh ich in turn may have a paracrine function on mantle cells of the islet .