Methoxsalen stimulates electrogenic Cl- secretion in the mouse jejunum.
We used the short-circuit current (I(sc)) 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 I(sc) 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 I(sc); however, clotrimazole, an intermediate Ca2(+)-activated K+ channel (IK(Ca)) blocker, reduced the MTX-stimulated I(sc). MTX did not alter Na(+)-glucose cotransport across the mouse jejunum. In cell-attached membrane patches, MTX increased the open probability of the basolateral IK(Ca) channel of isolated crypts. These data suggest that the CFTR and IK(Ca) channels participate in the MTX-activated, sustained Cl- secretory response of the mouse jejunum.
Hamilton
Kirk L
KL
Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand. kirk.hamilton@stonebow.otago.ac.nz
Butt
A Grant
AG
Cheng
Samantha
S
Carter
Derek J
DJ
D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D002034:Bumetanide / Q000008:administration & dosage / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008730:Methoxsalen / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
D015221:Potassium Channels; D002034:Bumetanide; D005576:Colforsin; D001464:Barium; D002713:Chlorine; D005905:Glyburide; D008730:Methoxsalen