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Methoxsalen stimulates electrogenic Cl− secretion in the mouse jejunum

Published online by Cambridge University Press:  25 June 2002

Kirk L. Hamilton ,
A. Grant Butt ,
Samantha Cheng  and
Derek J. Carter
Kirk L. Hamilton*
Affiliation:
Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand
A. Grant Butt
Affiliation:
Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand
Samantha Cheng
Affiliation:
Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand
Derek J. Carter
Affiliation:
Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand
*
Corresponding author: [email protected]
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Abstract

We used the short-circuit current (Isc) and patch-clamp techniques to investigate the effects of methoxsalen (MTX) on the electrogenic Cl− secretion of the mouse jejunum. MTX stimulated a sustained increase in Isc that was dose dependent. Bumetanide inhibited MTX-stimulated Isc in a dose-dependent manner consistent with activation of Cl− secretion. MTX failed to stimulate Isc following maximal activation of the cAMP pathway by forskolin, but did increase Isc after a submaximal dose of forskolin. Glibenclamide, a blocker of the cystic fibrosis transmembrane conductance regulator (CFTR), reduced the MTX-stimulated increase of Isc by 59 ± 6%. The cAMP-dependent K+ channel blocker 293B did not alter the MTX-activated Isc; however, clotrimazole, an intermediate Ca2+-activated K+ channel (IKCa) blocker, reduced the MTX-stimulated Isc. MTX did not alter Na+–glucose cotransport across the mouse jejunum.In cell-attached membrane patches, MTX increased the open probability of the basolateral IKCa channel of isolated crypts. These data suggest that the CFTR and IKCa channels participate in the MTX-activated, sustained Cl− secretory response of the mouse jejunum.

Type
Research Article
Information
Experimental Physiology , Volume 87 , Issue 4 , July 2002 , pp. 437 - 445
Copyright
Copyright © Experimental Physiology 2002

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