PMID- 16536741 OWN - NLM STAT- MEDLINE DCOM- 20060726 LR - 20131121 IS - 1398-9219 (Print) IS - 1398-9219 (Linking) VI - 7 IP - 4 DP - 2006 Apr TI - Extracellular ATP stimulates exocytosis via localized Ca(2+) release from acidic stores in rat pancreatic beta cells. PG - 429-39 AB - Three different methods, membrane capacitance (C(m)) measurement, amperometry and FM dye labeling were used to investigate the role of extracellular ATP in insulin secretion from rat pancreatic beta cells. We found that extracellular application of ATP mobilized intracellular Ca(2+) stores and synchronously triggered vigorous exocytosis. No influence of ATP on the readily releasable pool of vesicles was observed, which argues against a direct modulation of the secretory machinery at a level downstream of Ca(2+) elevation. The stimulatory effects of ATP were greatly reduced by intracellular perfusion of BAPTA but not EGTA, suggesting a close spatial association of fusion sites with intracellular Ca(2+) releasing sites. ATP-induced Ca(2+) transients and exocytosis were not blocked by thapsigargin (TG), by a ryanodine receptor antagonist or by dissipation of pH in acidic stores by monensin alone, but they were greatly attenuated by IP(3) receptor inhibition as well as ionomycin plus monensin, suggesting involvement of IP(3)-sensitive acidic Ca(2+) stores. Taken together, our data suggest that extracellular ATP triggers exocytosis by mobilizing spatially limited acidic Ca(2+) stores through IP(3) receptors. This mechanism may explain how insulin secretion from the pancreas is coordinated through diffusible ATP that is co-released with insulin. FAU - Xie, Li AU - Xie L AD - Joint Laboratory of Institute of Biophysics and Huazhong University of Science and Technology, National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China. FAU - Zhang, Ming AU - Zhang M FAU - Zhou, Wei AU - Zhou W FAU - Wu, Zhengxing AU - Wu Z FAU - Ding, Jiuping AU - Ding J FAU - Chen, Liangyi AU - Chen L FAU - Xu, Tao AU - Xu T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Traffic JT - Traffic (Copenhagen, Denmark) JID - 100939340 RN - 0 (Calcium Channels) RN - 0 (Enzyme Inhibitors) RN - 0 (FM1 43) RN - 0 (Fluorescent Dyes) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 0 (Insulin) RN - 0 (Muscle Relaxants, Central) RN - 0 (Pyridinium Compounds) RN - 0 (Quaternary Ammonium Compounds) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Purinergic P2) RN - 0 (Ryanodine Receptor Calcium Release Channel) RN - 3G6A5W338E (Caffeine) RN - 67526-95-8 (Thapsigargin) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - F64QU97QCR (Dantrolene) RN - SY7Q814VUP (Calcium) SB - IM MH - Adenosine Triphosphate/*metabolism MH - Animals MH - Caffeine/metabolism MH - Calcium/*metabolism MH - Calcium Channels/metabolism MH - Cells, Cultured MH - Dantrolene/metabolism MH - Electrophysiology MH - Enzyme Inhibitors/metabolism MH - Exocytosis/*physiology MH - Fluorescent Dyes/metabolism MH - *Hydrogen-Ion Concentration MH - Inositol 1,4,5-Trisphosphate Receptors MH - Insulin/*metabolism MH - Insulin-Secreting Cells/cytology/*metabolism MH - Male MH - Muscle Relaxants, Central/metabolism MH - Pyridinium Compounds/metabolism MH - Quaternary Ammonium Compounds/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - Receptors, Purinergic P2/metabolism MH - Ryanodine Receptor Calcium Release Channel/metabolism MH - Thapsigargin/metabolism EDAT- 2006/03/16 09:00 MHDA- 2006/07/27 09:00 CRDT- 2006/03/16 09:00 PHST- 2006/03/16 09:00 [pubmed] PHST- 2006/07/27 09:00 [medline] PHST- 2006/03/16 09:00 [entrez] AID - TRA401 [pii] AID - 10.1111/j.1600-0854.2006.00401.x [doi] PST - ppublish SO - Traffic. 2006 Apr;7(4):429-39. doi: 10.1111/j.1600-0854.2006.00401.x.