PMID- 11292458
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20191210
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 898
IP  - 1
DP  - 2001 Apr 13
TI  - Down-regulation of cell surface insulin receptors by sarco(endo)plasmic reticulum 
      Ca2+-ATPase inhibitor in adrenal chromaffin cells.
PG  - 152-7
AB  - Long-term (> or =12 h) treatment of cultured bovine adrenal chromaffin cells with 
      thapsigargin (TG), an inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPase 
      (SERCA), caused a time (t(1/2)=16.3 h)- and concentration (IC50=37.8 
      nM)-dependent decrease of cell surface 125I-insulin binding by 35%, but did not 
      change the Kd value. TG caused a sustained increase of cytoplasmic concentration 
      of Ca2+ ([Ca2+]c) in a biphasic manner, and the effect of TG on 125I-insulin 
      binding was abolished by BAPTA-AM. Western blot analysis showed that TG lowered 
      insulin receptor (IR) beta-subunit level in membrane, but did not alter total 
      cellular levels of IR precursor and IR beta-subunit. Internalization of cell 
      surface IR, as measured by using brefeldin A, an inhibitor of vesicular exit from 
      the trans-Golgi network (TGN), was not changed by TG. These results suggest that 
      inhibition of SERCA by TG and the subsequent increase of [Ca2+]c down-regulates 
      cell surface IR by retarding externalization of IR from the TGN.
FAU - Shiraishi, S
AU  - Shiraishi S
AD  - Department of Pharmacology, Miyazaki Medical College, 889-1692, Miyazaki, Japan.
FAU - Yamamoto, R
AU  - Yamamoto R
FAU - Yanagita, T
AU  - Yanagita T
FAU - Yokoo, H
AU  - Yokoo H
FAU - Kobayashi, H
AU  - Kobayashi H
FAU - Uezono, Y
AU  - Uezono Y
FAU - Wada, A
AU  - Wada A
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Chelating Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid 
      acetoxymethyl ester)
RN  - 20350-15-6 (Brefeldin A)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adrenal Glands/cytology/*metabolism
MH  - Animals
MH  - Brefeldin A/pharmacology
MH  - Calcium/metabolism
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - Cattle
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Chelating Agents/pharmacology
MH  - Chromaffin Cells/*metabolism
MH  - Cytoplasm/metabolism
MH  - Down-Regulation
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Insulin/metabolism
MH  - Osmolar Concentration
MH  - Receptor, Insulin/*metabolism
MH  - Sarcoplasmic Reticulum/*enzymology
MH  - Thapsigargin/*pharmacology
MH  - Time Factors
EDAT- 2001/04/09 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/04/09 10:00
PHST- 2001/04/09 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/04/09 10:00 [entrez]
AID - S0006-8993(01)02193-X [pii]
AID - 10.1016/s0006-8993(01)02193-x [doi]
PST - ppublish
SO  - Brain Res. 2001 Apr 13;898(1):152-7. doi: 10.1016/s0006-8993(01)02193-x.