PMID- 12504118
OWN - NLM
STAT- MEDLINE
DCOM- 20030225
LR  - 20190612
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 300
IP  - 2
DP  - 2003 Jan 10
TI  - Relationship between a HCO3- -permeable conductance and a CLCA protein from rat 
      pancreatic zymogen granules.
PG  - 546-54
AB  - Ca(2+)-induced enzyme secretion in the exocrine pancreas is not completely 
      understood. We have proposed that Ca(2+)-induced enzyme secretion in the exocrine 
      pancreas involves activation of ion conductances in the membrane of zymogen 
      granules (ZG). Here we have identified a Ca(2+)-activated anion conductance in 
      rat pancreatic ZG membranes (ZGM). Ca(2+) (2.5-50 microM) increased the 
      conductance for I(-), NO(3)(-), Br(-), or HCO(3)(-), but not for Cl(-), as 
      determined by the rate of valinomycin-induced osmotic lysis of ZG suspended in 
      isotonic K(+)-salts. 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulfonate (100 
      microM) or 25 microM dithiothreitol strongly inhibited Ca(2+)-dependent lysis. 
      The permeability sequence, Ca(2+) dependence, and inhibitor sensitivity of ZG 
      anion conductance are reminiscent of a family of epithelial Ca(2+)-activated 
      anion channels (CLCA). CLCA expression was confirmed by RT-PCR with rat 
      pancreatic mRNA and mouse CLCA1 primers. A PCR product (580bp) exhibited 81%, 
      77%, and 57% amino acid similarity to the three mouse isoforms mCLCA-1, -2, and 
      -3 (mgob-5), respectively. Antibodies against bovine tracheal CLCA1 showed CLCA 
      expression in ZGM by immunoblotting, immunoperoxidase light microscopy, and 
      immunogold labeling. These findings suggest that a CLCA-related protein could 
      account for the Ca(2+)-activated HCO(3)(-) conductance of rat pancreatic ZGM and 
      contribute to hormone-stimulated enzyme secretion.
FAU - Thevenod, Frank
AU  - Thevenod F
AD  - Department of Physiology and Pathophysiology, Medical Faculty, University of 
      Witten/Herdecke, Stockumer Strasse 12, Thyssenhaus, D-58448 Witten, Germany. 
      frank.thevenod@uni-wh.de
FAU - Roussa, Eleni
AU  - Roussa E
FAU - Benos, Dale J
AU  - Benos DJ
FAU - Fuller, Catherine M
AU  - Fuller CM
LA  - eng
GR  - DK 53090/DK/NIDDK NIH HHS/United States
GR  - DK 53480/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Bicarbonates)
RN  - 0 (Chloride Channels)
RN  - 61481-03-6 (dihydro-DIDS)
RN  - Q1O6DSW23R (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid)
RN  - SY7Q814VUP (Calcium)
RN  - T8ID5YZU6Y (Dithiothreitol)
SB  - IM
MH  - 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/*analogs & 
      derivatives/pharmacology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bicarbonates/*metabolism
MH  - Calcium/pharmacology
MH  - Chloride Channels/analysis/genetics/*physiology
MH  - Dithiothreitol/pharmacology
MH  - Electric Conductivity
MH  - Exocytosis
MH  - Intracellular Membranes/chemistry
MH  - Ion Transport
MH  - Male
MH  - Molecular Sequence Data
MH  - Pancreas/cytology/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Secretory Vesicles/chemistry/*metabolism/ultrastructure
MH  - Sequence Alignment
EDAT- 2002/12/31 04:00
MHDA- 2003/02/26 04:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/02/26 04:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0006291X02028711 [pii]
AID - 10.1016/s0006-291x(02)02871-1 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2003 Jan 10;300(2):546-54. doi: 
      10.1016/s0006-291x(02)02871-1.