PMID- 8621734
OWN - NLM
STAT- MEDLINE
DCOM- 19960619
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 6
DP  - 1996 Feb 9
TI  - Chloride and potassium conductances of mouse pancreatic zymogen granules are
      inversely regulated by a approximately 80-kDa mdr1a gene product.
PG  - 3300-5
AB  - Cl- and cation conductances were characterized in zymogen granules (ZG) isolated 
      from the pancreas of wild-type mice (+/+) or mice with a homozygous disruption of
      the multidrug resistance P-glycoprotein gene mdr1a (-/-). Cl- conductance of ZG
      was assayed in isotonic KCl buffer by measuring osmotic lysis, which was induced 
      by maximal permeabilization of ZG membranes (ZGM) for K+ with valinomycin due to 
      influx of K+ through the artificial pathway and of Cl- through endogenous
      channels. To measure cation conductances, ZG (pHi 6.0-6.5) were suspended in
      buffered isotonic monovalent cation acetate solutions (pH 7.0). The pH gradient
      was converted into an outside-directed H+ diffusion potential by maximally
      increasing H+ conductance of ZGM with carbonyl cyanide m-chlorophenylhydrazone.
      Osmotic lysis of ZG was induced by H+ diffusion potential-driven influx of
      monovalent cations through endogenous channels and nonionic diffusion of the
      counterion acetate. ZGM Cl- conductances were not different in (-/-) and (+/+)
      mice (2.6 +/- 0.3 h-1 versus 3.1 +/- 0.2 h-1 (relative rate constant)). The
      nonhydrolyzable ATP analog adenosine 5'-(beta,gamma-methylene)triphosphate
      (AMP-PCP) (0.5 mM) activated the Cl- conductance both in (+/+) and (-/-) mice.
      However, activation of Cl- conductance by AMP-PCP was reduced in (-/-) mice as
      compared with (+/+) mice (5.0 +/- 0.4 h-1 versus 7.6 +/- 0.7 h-1; p < 0. 005). In
      contrast, ZGM K+ conductance was increased in (-/-) mice as compared with (+/+)
      mice (14.2 +/- 2.0 h-1 versus 8.5 +/- 1.2 h-1; p < 0.03). In the presence of 0.5 
      mm AMP-PCP, which completely blocks K+ conductance but leaves a nonselective
      cation conductance unaffected, there was no difference between (-/-) and (+/+)
      mice (5.3 +/- 0.7 h-1 versus 3.2 +/- 0.5 h-1). In Western blots of ZGM from
      wild-type mice, a polyclonal MDR1 specific antibody labeled a protein band of
      approximately 80 kDa. In mdr1a-deficient mice, the intensity of this band was
      reduced to 39 +/- 7% of the wild-type signal. This indicates that a mdr1a gene
      product of approximately 80 kDa enhances the AMP-PCP-activated fraction of mouse 
      ZGM Cl- conductance and reduces AMP-PCP-sensitive K+ conductance.
FAU - Thevenod, F
AU  - Thevenod F
AD  - II Department of Physiology, Medical Faculty, University of Saarland, 66421
      Homburg/Saar, Federal Republic of Germany.
FAU - Hildebrandt, J P
AU  - Hildebrandt JP
FAU - Striessnig, J
AU  - Striessnig J
FAU - de Jonge, H R
AU  - de Jonge HR
FAU - Schulz, I
AU  - Schulz I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antibodies)
RN  - 0 (Chloride Channels)
RN  - 0 (Chlorides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Potassium Channels)
RN  - 3469-78-1 (5'-adenylyl (beta,gamma-methylene)diphosphonate)
RN  - 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - NYX13NT29D (alpha,beta-methyleneadenosine 5'-triphosphate)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member
      1/*deficiency/genetics/*physiology
MH  - Adenosine Triphosphate/analogs & derivatives/pharmacology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies
MH  - Biological Transport/drug effects
MH  - Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology
MH  - Chloride Channels/*physiology
MH  - Chlorides/*metabolism
MH  - Cytoplasmic Granules/drug effects/*physiology
MH  - Drug Resistance, Multiple/*genetics
MH  - Humans
MH  - Intracellular Membranes/drug effects/physiology
MH  - Kinetics
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Pancreas/*physiology
MH  - Peptide Fragments/chemistry/immunology
MH  - Potassium/*metabolism
MH  - Potassium Channels/*physiology
EDAT- 1996/02/09 00:00
MHDA- 1996/02/09 00:01
CRDT- 1996/02/09 00:00
PHST- 1996/02/09 00:00 [pubmed]
PHST- 1996/02/09 00:01 [medline]
PHST- 1996/02/09 00:00 [entrez]
AID - 10.1074/jbc.271.6.3300 [doi]
AID - S0021-9258(18)98011-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1996 Feb 9;271(6):3300-5. doi: 10.1074/jbc.271.6.3300.