Document Detail

Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.
MedLine Citation:
PMID:  25177167     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.
Han-Yi Jiao; Dong Hyun Kim; Jung Suk Ki; Kwon Ho Ryu; Seok Choi; Jae Yeoul Jun
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Publication Detail:
Type:  Journal Article     Date:  2014-08-13
Journal Detail:
Title:  The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology     Volume:  18     ISSN:  1226-4512     ISO Abbreviation:  Korean J. Physiol. Pharmacol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-09-01     Completed Date:  2014-09-01     Revised Date:  2014-09-03    
Medline Journal Info:
Nlm Unique ID:  9709505     Medline TA:  Korean J Physiol Pharmacol     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  341-6     Citation Subset:  -    
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