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Methoxsalen stimulates electrogenic C1 − secretion in the mouse jejunum
Author(s) -
Hamilton Kirk L.,
Butt A. Grant,
Cheng Samantha,
Carter Derek J.
Publication year - 2002
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2002.tb00056.x
Subject(s) - forskolin , bumetanide , cystic fibrosis transmembrane conductance regulator , endocrinology , medicine , jejunum , chemistry , cotransporter , glibenclamide , channel blocker , secretion , methoxsalen , pharmacology , ion transporter , biology , biochemistry , stimulation , cystic fibrosis , immunology , membrane , calcium , psoriasis , organic chemistry , diabetes mellitus , sodium
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 I sc that was dose dependent. Bumetanide inhibited MTX‐stimulated I sc 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 I sc after a submaximal dose of forskolin. Glibenclamide, a blocker of the cystic fibrosis transmembrane conductance regulator (CFTR), reduced the MTX‐stimulated increase of I sc by 59 ± 6%. The cAMP‐dependent K + channel blocker 293B did not alter the MTX‐activated I sc ; however, clotrimazole, an intermediate Ca 2+ ‐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.