HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/G650    most recent 00376.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Bachmann, O. Articles by Seidler, U. Search for Related Content PubMed PubMed Citation Articles by Bachmann, O. Articles by Seidler, U.

MUCOSAL BIOLOGY

Carbachol increases Na⁺-HCO₃^– cotransport activity in murine colonic crypts in a M₃^–, Ca²⁺/calmodulin-, and PKC-dependent manner

Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany

Submitted 12 August 2005 ; accepted in final form 25 April 2006

The Na⁺-HCO₃^– cotransporter (NBC) mediates HCO₃^– import into the colonocyte via its pNBC1 isoform. Whereas renal kNBC1 is inhibited by increased cAMP levels, pNBC1 is stimulated. Cholinergic stimulation activates renal NBC, but the effect on intestinal NBC is unknown. Therefore, crypts were isolated from the murine proximal colon by Ca²⁺ chelation and loaded with the pH-sensitive dye 2',7'-bis-carboxyethyl-5,6-carboxyfluorescein. Na⁺-HCO₃^– cotransport activity was calculated from the dimethylamiloride-insensitive (500 µM) intracellular pH recovery from an acid load in the presence of CO₂-HCO₃^– and the intracellular buffering capacity. Carbachol strongly increased Na⁺-HCO₃^– cotransport activity compared with control rates. Ca²⁺ chelation with BAPTA-AM, blockade of the M₃ subtype of muscarinergic receptors with 4-diphenylacetoxy-N-methylpiperidine methiodide, and inhibition of Ca²⁺/calmodulin kinase II with KN-62 all caused significant inhibition of the carbachol-induced NBC activity increase. Furthermore, PKC inhibition with Gö-6976 and Gö-6850 significantly reduced the carbachol effect, which may be related to the unique NH₂-terminal consensus site for PKC-dependent phosphorylation of pNBC1. We conclude that NBC in the murine colon is thus activated by carbachol, consistent with its presumed function as an anion uptake pathway during intestinal anion secretion, but that the signal transductions pathways are distinct from those involved in the cholinergic activation of renal NBC1.

colon; anion secretion; ion transport; intestinal epithelium

This article has been cited by other articles:

				E. Ohana, D. Yang, N. Shcheynikov, and S. Muallem Diverse transport modes by the solute carrier 26 family of anion transporters J. Physiol., May 15, 2009; 587(10): 2179 - 2185. [Abstract] [Full Text] [PDF]

				X. Dong, E. J. Smoll, K. H. Ko, J. Lee, J. Y. Chow, H. D. Kim, P. A. Insel, and H. Dong P2Y receptors mediate Ca2+ signaling in duodenocytes and contribute to duodenal mucosal bicarbonate secretion Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G424 - G432. [Abstract] [Full Text] [PDF]

				C. Perry, D. O. Quissell, M. E. Reyland, and I. I. Grichtchenko Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1385 - C1398. [Abstract] [Full Text] [PDF]

				C. Perry, H. Le, and I. I. Grichtchenko ANG II and calmodulin/CaMKII regulate surface expression and functional activity of NBCe1 via separate means Am J Physiol Renal Physiol, July 1, 2007; 293(1): F68 - F77. [Abstract] [Full Text] [PDF]