AJP - GI Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 275: G1274-G1281, 1998;
0193-1857/98 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mall, M.
Right arrow Articles by Kunzelmann, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mall, M.
Right arrow Articles by Kunzelmann, K.
Vol. 275, Issue 6, G1274-G1281, December 1998

Cholinergic ion secretion in human colon requires coactivation by cAMP

M. Mall1,2, M. Bleich1, M. Schürlein2, J. Kühr2, H. H. Seydewitz2, M. Brandis2, R. Greger1, and K. Kunzelmann1

1 Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg; and 2 Kinderklinik der Albert-Ludwigs-Universität Freiburg, D-79106 Freiburg, Germany

Cl- secretion in the colon can be activated by an increase of either intracellular Ca2+ or cAMP. In this study we examined a possible interdependence of the two second-messenger pathways in human colonic epithelium. When measured in a modified Ussing chamber, carbachol (CCH; 100 µmol/l, basolateral), via an increase in cytosolic Ca2+ concentration ([Ca2+]i), activated a transient lumen-negative equivalent short-circuit current (Isc) [change (Delta ) in Isc = -79.4 ± 7.5 µA/cm2]. Previous studies indicated that intracellular Ca2+ directly acts on basolateral K+ channels, thus enhancing driving force for luminal Cl- exit. Increased intracellular cAMP (by basolateral addition of 100 µmol/l IBMX and 1 µmol/l forskolin) activated a sustained lumen-negative current (Delta Isc = -42.4 ± 7.2 µA/cm2) that was inhibited by basolateral trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl&2-chromane (10 µmol/l), a blocker of KvLQT1 channels. In the presence of elevated cAMP, the CCH-activated currents were augmented (Delta Isc = 167.7 ± 32.7 µA/cm2), suggesting cooperativity of the Ca2+- and cAMP-mediated responses. Inhibition of endogenous cAMP production by indomethacin (10 µmol/l) significantly reduced CCH-activated currents and even reversed the polarity in 70% of the experiments. The transient lumen-positive Isc was probably due to activation of apical K+ channels because it was blocked by luminal Ba2+ (5 mmol/l) and tetraethylammonium (10 mmol/l). In the presence of indomethacin (10 µmol/l, basolateral), an increase of cAMP activated a sustained negative Isc. Under these conditions, CCH induced a large further increase in lumen-negative Isc (Delta Isc = -100.0 ± 21.0 µA/cm2). We conclude that CCH acting via [Ca2+]i can induce Cl- secretion only in the presence of cAMP, i.e., when luminal Cl- channels are already activated. The activation of a luminal and basolateral K+ conductance by CCH may be essential for transepithelial KCl secretion in human colon.

cystic fibrosis transmembrane conductance regulator; epithelial transport; potassium channels; Ussing chamber; microelectrodes; transepithelial voltage; carbachol


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
D. Heitzmann and R. Warth
Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia
Physiol Rev, July 1, 2008; 88(3): 1119 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
C. A. Flores, J. E. Melvin, C. D. Figueroa, and F. V. Sepulveda
Abolition of Ca2+-mediated intestinal anion secretion and increased stool dehydration in mice lacking the intermediate conductance Ca2+-dependent K+ channel Kcnn4
J. Physiol., September 1, 2007; 583(2): 705 - 717.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
A. Reynolds, A. Parris, L. A. Evans, S. Lindqvist, P. Sharp, M. Lewis, R. Tighe, and M. R. Williams
Dynamic and differential regulation of NKCC1 by calcium and cAMP in the native human colonic epithelium
J. Physiol., July 15, 2007; 582(2): 507 - 524.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. T. Halm, T. Liao, and D. R. Halm
Distinct K+ conductive pathways are required for Cl- and K+ secretion across distal colonic epithelium
Am J Physiol Cell Physiol, October 1, 2006; 291(4): C636 - C648.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Ohashi, Y. Ito, T. Matsuno, S. Sato, K. Shimokata, and H. Kume
Paradoxical Effects of Hydrogen Peroxide on Human Airway Anion Secretion
J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 296 - 303.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. Liao, L. Wang, S. T. Halm, L. Lu, R. E. W. Fyffe, and D. R. Halm
K+ channel KVLQT1 located in the basolateral membrane of distal colonic epithelium is not essential for activating Cl- secretion
Am J Physiol Cell Physiol, September 1, 2005; 289(3): C564 - C575.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. J. Joiner, S. Basavappa, S. Vidyasagar, K. Nehrke, S. Krishnan, H. J. Binder, E. L. Boulpaep, and V. M. Rajendran
Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon
Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G185 - G196.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Hayashi, T. Suzuki, T. Yamamoto, and Y. Suzuki
Cholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colon
Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G617 - G628.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Hosoda, S.-I. Karaki, Y. Shimoda, and A. Kuwahara
Substance P-evoked Cl- secretion in guinea pig distal colonic epithelia: interaction with PGE2
Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G347 - G356.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-L. Ji, B. Jovov, J. Fu, L. R. Bishop, H. C. Mebane, C. M. Fuller, B. A. Stanton, and D. J. Benos
Up-regulation of Acid-gated Na+ Channels (ASICs) by Cystic Fibrosis Transmembrane Conductance Regulator Co-expression in Xenopus Oocytes
J. Biol. Chem., March 1, 2002; 277(10): 8395 - 8405.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Mall, T. Gonska, J. Thomas, S. Hirtz, R. Schreiber, and K. Kunzelmann
Activation of ion secretion via proteinase-activated receptor-2 in human colon
Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G200 - G210.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
K. Kunzelmann and M. Mall
Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease
Physiol Rev, January 1, 2002; 82(1): 245 - 289.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Mall, A. Wissner, R. Schreiber, J. Kuehr, H. H. Seydewitz, M. Brandis, R. Greger, and K. Kunzelmann
Role of KVLQT1 in Cyclic Adenosine Monophosphate-Mediated Cl- Secretion in Human Airway Epithelia
Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 283 - 289.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Mall, A. Wissner, H. H. Seydewitz, J. Kuehr, M. Brandis, R. Greger, and K. Kunzelmann
Defective cholinergic Cl- secretion and detection of K+ secretion in rectal biopsies from cystic fibrosis patients
Am J Physiol Gastrointest Liver Physiol, April 1, 2000; 278(4): G617 - G624.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Mall, M. Bleich, J. Kuehr, M. Brandis, R. Greger, and K. Kunzelmann
CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis
Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G709 - G716.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. R. Grubb
Ion transport across the normal and CF neonatal murine intestine
Am J Physiol Gastrointest Liver Physiol, July 1, 1999; 277(1): G167 - G174.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. W. Cuthbert, M. E. Hickman, P. Thorn, and L. J. MacVinish
Activation of Ca2+- and cAMP-sensitive K+ channels in murine colonic epithelia by 1-ethyl-2-benzimidazolone
Am J Physiol Cell Physiol, July 1, 1999; 277(1): C111 - C120.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
W. H. Ko, V. W. Y. Law, W. C. Y. Yip, G. G. L. Yue, C. W. Lau, Z. Y. Chen, and Y. Huang
Stimulation of chloride secretion by baicalein in isolated rat distal colon
Am J Physiol Gastrointest Liver Physiol, March 1, 2002; 282(3): G508 - G518.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online