Xanthine derivatives without PDE effect stimulate voltage-activated chloride conductance of toad skin
1 Department of Physiology, University of Munich, 80336 Munich, Germany; and 2 Department of Biology, Technion, Haifa, Israel The effect of xanthine derivatives on the voltage-activated Cl conductance ( G Cl ) of amphibian skin was analyzed. 3-Isobutyl-1-methylxanthine (IBMX) and the recently synt...
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Published in | American Journal of Physiology: Cell Physiology Vol. 284; no. 2; p. C521 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
01.02.2003
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Online Access | Get full text |
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Summary: | 1 Department of Physiology, University of Munich,
80336 Munich, Germany; and 2 Department
of Biology, Technion, Haifa, Israel
The effect of xanthine derivatives
on the voltage-activated Cl conductance
( G Cl ) of amphibian skin was analyzed.
3-Isobutyl-1-methylxanthine (IBMX) and the recently synthesized
xanthine derivatives 3,7-dimethyl-1-propyl xanthine (X-32) and
3,7-dimethyl-1-isobutyl xanthine (X-33), which lack inhibitory effects
on phosphodiesterases in CHO and Calu-3 cells, increased
voltage-activated G Cl without effect on baseline conductance at inactivating voltage. Half-maximal stimulation of
G Cl occurred at 108 ± 9 µM for X-32 and
X-33 after apical or basolateral application. The stimulation of
G Cl , which occurs only in the presence of
Cl in the mucosal solution, is caused by a shift of the
voltage sensitivity to lower clamp potentials and an increase of the
maximally activated level. Furosemide reversed both the shift of
sensitivity and the increase in magnitude. These patterns are
fundamentally different from those seen after application of
membrane-permeant, nonmetabolized analogs of cAMP, and they indicate
that the xanthines stimulate G Cl directly. This
notion is strengthened by the lack of influence on intracellular cAMP
content, which is consistent with the observations in CHO and Calu-3
cells. We propose that the xanthine derivatives increase the voltage
sensitivity of a regulative component in the conductive
Cl pathway across amphibian skin.
Bufo viridis ; furosemide; 3-isobutyl-1-methylxanthine; mitochondria-rich cells |
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ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.00276.2002 |