PMID- 30273839
OWN - NLM
STAT- MEDLINE
DCOM- 20190809
LR  - 20190809
IS  - 1532-1991 (Electronic)
IS  - 0143-4160 (Linking)
VI  - 76
DP  - 2018 Dec
TI  - Lysosomal exocytosis of ATP is coupled to P2Y(2) receptor in marginal cells in 
      the stria vascular in neonatal rats.
PG  - 62-71
LID - S0143-4160(18)30125-8 [pii]
LID - 10.1016/j.ceca.2018.09.006 [doi]
AB  - Adenosine triphosphate (ATP) is stored as lysosomal vesicles in marginal cells of 
      the stria vascular in neonatal rats, but the mechanisms of ATP release are 
      unclear. Primary cultures of marginal cells from 1-day-old Sprague-Dawley rats 
      were established. P2Y(2) receptor and inositol 1,4,5-trisphosphate (IP3) receptor 
      were immunolabelled in marginal cells of the stria vascular. We found that 30 muM 
      ATP and 30 muM uridine triphosphate (UTP) evoked comparable significant increases 
      in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence of 
      extracellular Ca(2+), whereas the response was suppressed by 100 muM suramin, 
      10 muM 
      1-(6-(17beta-3-methoxyester-1,3,5(10)-trien-17-yl)amino)-hexyl)-1H-pyrrole-2,5-dione(U-73122), 
      100 muM 2-aminoethoxydiphenyl borate (2-APB) and 5 muM thapsigargin (TG), thus 
      indicating that ATP coupled with the P2Y(2)R-PLC-IP3 pathway to evoke Ca(2+) 
      release from the endoplasmic reticulum (ER). Incubation with 
      200 muM Gly-Phe-beta-naphthylamide (GPN) selectively disrupted lysosomes and caused 
      significant increases in [Ca(2+)](I); this effect was partly inhibited by 
      P2Y(2)R-PLC-IP3 pathway antagonists. After pre-treatment with 5 muM TG, 
      [Ca(2+)](i) was significantly lower than that after treatment with 
      P2Y(2)R-PLC-IP3 pathway antagonists under the same conditions, thus indicating 
      that lysosomal Ca(2+) triggers Ca(2+) release from ER Ca(2+) stores. Baseline 
      [Ca(2+)](i) declined after treatment with the Ca(2+) chelator 
      50 muM bis-(aminophenolxy) ethane-N,N,N',N'-tetra-acetic acid acetoxyme-thyl ester 
      (BAPTA-AM) and 4 IU/ml apyrase. 30 muM ATP decrease of the number of 
      quinacrine-positive vesicles via lysosome exocytosis, whereas the number of 
      lysosomes did not change. However, lysosome exocytosis was significantly 
      suppressed by pre-treatment with 5 muM vacuolin-1. Release of ATP and 
      beta-hexosaminidase both increased after treatment with 200 muM GPN and 5 muM TG, but 
      decreased after incubation with 50 muM BAPTA-AM, 4 IU/ml apyrase and 
      5 muM vacuolin-1. We suggest that ATP triggers Ca(2+) release from the ER, thereby 
      contributing to secretion of lysosomal ATP via lysosomal exocytosis. Lysosomal 
      stored Ca(2+) triggers Ca(2+) release from the ER directly though the IP3 
      receptors, and lysosomal ATP evokes Ca(2+) signals indirectly via the 
      P2Y(2)R-PLC-IP3 pathway.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Liu, Bin
AU  - Liu B
AD  - Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China.
FAU - Cao, Wanxin
AU  - Cao W
AD  - Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China.
FAU - Li, Jiping
AU  - Li J
AD  - Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China. Electronic address: drlijiping@163.com.
FAU - Liu, Jun
AU  - Liu J
AD  - Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai, China. Electronic address: liujun1220@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180921
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 0 (vacuolin-1)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
MH  - Adenosine Triphosphate/antagonists & inhibitors/*metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Calcium/metabolism
MH  - Endoplasmic Reticulum/drug effects/metabolism
MH  - *Exocytosis/drug effects
MH  - Heterocyclic Compounds, 4 or More Rings/pharmacology
MH  - Lysosomes/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Purinergic P2Y2/*metabolism
OTO - NOTNLM
OT  - Adenosine triphosphate
OT  - Calcium
OT  - Lysosomal exocytosis
OT  - P2Y(2)R-PLC-IP3 pathway
EDAT- 2018/10/03 06:00
MHDA- 2019/08/10 06:00
CRDT- 2018/10/02 06:00
PHST- 2018/07/12 00:00 [received]
PHST- 2018/09/09 00:00 [revised]
PHST- 2018/09/20 00:00 [accepted]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2019/08/10 06:00 [medline]
PHST- 2018/10/02 06:00 [entrez]
AID - S0143-4160(18)30125-8 [pii]
AID - 10.1016/j.ceca.2018.09.006 [doi]
PST - ppublish
SO  - Cell Calcium. 2018 Dec;76:62-71. doi: 10.1016/j.ceca.2018.09.006. Epub 2018 Sep 
      21.