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Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon
Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secreti...
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| Published in: | American journal of physiology: Gastrointestinal and liver physiology 2009-04, Vol.296 (4), p.G823-G832 |
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| container_end_page | G832 |
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| container_title | American journal of physiology: Gastrointestinal and liver physiology |
| container_volume | 296 |
| creator | Fei, Guijun Wang, Yu-Zhong Liu, Sumei Hu, Hong-Zhen Wang, Guo-Du Qu, Mei-Hua Wang, Xi-Yu Xia, Yun Sun, Xiaohong Bohn, Laura M Cooke, Helen J Wood, Jackie D |
| description | Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P |
| doi_str_mv | 10.1152/ajpgi.90447.2008 |
| format | article |
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Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.</description><identifier>ISSN: 0193-1857</identifier><identifier>EISSN: 1522-1547</identifier><identifier>DOI: 10.1152/ajpgi.90447.2008</identifier><identifier>PMID: 19179625</identifier><identifier>CODEN: APGPDF</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Alprostadil - administration & dosage ; Alprostadil - analogs & derivatives ; Alprostadil - pharmacology ; Animals ; Biochemistry ; Biological Transport - drug effects ; Cathartics - pharmacology ; Chlorides - metabolism ; Colon ; Colon - drug effects ; Colon - metabolism ; Dose-Response Relationship, Drug ; Guinea Pigs ; Histamine - metabolism ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - metabolism ; Intestine, Small - drug effects ; Intestine, Small - metabolism ; Lubiprostone ; Mammals ; Membranes ; Mucosal Biology ; Neurons ; Neurons - physiology ; Prostaglandins - metabolism ; Small intestine</subject><ispartof>American journal of physiology: Gastrointestinal and liver physiology, 2009-04, Vol.296 (4), p.G823-G832</ispartof><rights>Copyright American Physiological Society Apr 2009</rights><rights>Copyright © 2009, American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-81fc899f6811f966038586af62a54f5a44011b6ee828b43dee6d421213bb63d93</citedby><cites>FETCH-LOGICAL-c487t-81fc899f6811f966038586af62a54f5a44011b6ee828b43dee6d421213bb63d93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19179625$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fei, Guijun</creatorcontrib><creatorcontrib>Wang, Yu-Zhong</creatorcontrib><creatorcontrib>Liu, Sumei</creatorcontrib><creatorcontrib>Hu, Hong-Zhen</creatorcontrib><creatorcontrib>Wang, Guo-Du</creatorcontrib><creatorcontrib>Qu, Mei-Hua</creatorcontrib><creatorcontrib>Wang, Xi-Yu</creatorcontrib><creatorcontrib>Xia, Yun</creatorcontrib><creatorcontrib>Sun, Xiaohong</creatorcontrib><creatorcontrib>Bohn, Laura M</creatorcontrib><creatorcontrib>Cooke, Helen J</creatorcontrib><creatorcontrib>Wood, Jackie D</creatorcontrib><title>Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon</title><title>American journal of physiology: Gastrointestinal and liver physiology</title><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><description>Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.</description><subject>Alprostadil - administration & dosage</subject><subject>Alprostadil - analogs & derivatives</subject><subject>Alprostadil - pharmacology</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological Transport - drug effects</subject><subject>Cathartics - pharmacology</subject><subject>Chlorides - metabolism</subject><subject>Colon</subject><subject>Colon - drug effects</subject><subject>Colon - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Guinea Pigs</subject><subject>Histamine - metabolism</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestine, Small - drug effects</subject><subject>Intestine, Small - metabolism</subject><subject>Lubiprostone</subject><subject>Mammals</subject><subject>Membranes</subject><subject>Mucosal Biology</subject><subject>Neurons</subject><subject>Neurons - physiology</subject><subject>Prostaglandins - metabolism</subject><subject>Small intestine</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpVkctLxDAQxoMouj7uniR40kPXTF5NL4KILxAU1HNI23TN0ia1aQX_e-O6-DgNfDPzzeOH0CGQOYCgZ2bZL9y8IJznc0qI2kCzJNMMBM830YxAwTJQIt9BuzEuCSGCAmyjHSggLyQVM1Q9ja6bWjO64HFocDdVIZoWR1sNdiWWH7idStcPIY7BW3zy9HiXkeRzip3Hi8l5a3DvFjh2pm2TNto4JhEbX-MqtMHvo63GtNEerOMeerm-er68ze4fbu4uL-6ziqt8zBQ0lSqKRiqAppCSMCWUNI2kRvBGGM4JQCmtVVSVnNXWyppToMDKUrK6YHvo_Nu3n8rO1pX142Ba3Q-uM8OHDsbp_xnvXvUivGsqcyIlSwbHa4MhvE3pDL0M0-DTzpoyKhQHoVIR-S6q0kfiYJufAUD0FxW9oqJXVPQXldRy9Hex34Y1BvYJ1cSJiw</recordid><startdate>20090401</startdate><enddate>20090401</enddate><creator>Fei, Guijun</creator><creator>Wang, Yu-Zhong</creator><creator>Liu, Sumei</creator><creator>Hu, Hong-Zhen</creator><creator>Wang, Guo-Du</creator><creator>Qu, Mei-Hua</creator><creator>Wang, Xi-Yu</creator><creator>Xia, Yun</creator><creator>Sun, Xiaohong</creator><creator>Bohn, Laura M</creator><creator>Cooke, Helen J</creator><creator>Wood, Jackie D</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20090401</creationdate><title>Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon</title><author>Fei, Guijun ; Wang, Yu-Zhong ; Liu, Sumei ; Hu, Hong-Zhen ; Wang, Guo-Du ; Qu, Mei-Hua ; Wang, Xi-Yu ; Xia, Yun ; Sun, Xiaohong ; Bohn, Laura M ; Cooke, Helen J ; Wood, Jackie D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-81fc899f6811f966038586af62a54f5a44011b6ee828b43dee6d421213bb63d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alprostadil - administration & dosage</topic><topic>Alprostadil - analogs & derivatives</topic><topic>Alprostadil - pharmacology</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological Transport - drug effects</topic><topic>Cathartics - pharmacology</topic><topic>Chlorides - metabolism</topic><topic>Colon</topic><topic>Colon - drug effects</topic><topic>Colon - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Guinea Pigs</topic><topic>Histamine - metabolism</topic><topic>Intestinal Mucosa - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestine, Small - drug effects</topic><topic>Intestine, Small - metabolism</topic><topic>Lubiprostone</topic><topic>Mammals</topic><topic>Membranes</topic><topic>Mucosal Biology</topic><topic>Neurons</topic><topic>Neurons - physiology</topic><topic>Prostaglandins - metabolism</topic><topic>Small intestine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fei, Guijun</creatorcontrib><creatorcontrib>Wang, Yu-Zhong</creatorcontrib><creatorcontrib>Liu, Sumei</creatorcontrib><creatorcontrib>Hu, Hong-Zhen</creatorcontrib><creatorcontrib>Wang, Guo-Du</creatorcontrib><creatorcontrib>Qu, Mei-Hua</creatorcontrib><creatorcontrib>Wang, Xi-Yu</creatorcontrib><creatorcontrib>Xia, Yun</creatorcontrib><creatorcontrib>Sun, Xiaohong</creatorcontrib><creatorcontrib>Bohn, Laura M</creatorcontrib><creatorcontrib>Cooke, Helen J</creatorcontrib><creatorcontrib>Wood, Jackie D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fei, Guijun</au><au>Wang, Yu-Zhong</au><au>Liu, Sumei</au><au>Hu, Hong-Zhen</au><au>Wang, Guo-Du</au><au>Qu, Mei-Hua</au><au>Wang, Xi-Yu</au><au>Xia, Yun</au><au>Sun, Xiaohong</au><au>Bohn, Laura M</au><au>Cooke, Helen J</au><au>Wood, Jackie D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2009-04-01</date><risdate>2009</risdate><volume>296</volume><issue>4</issue><spage>G823</spage><epage>G832</epage><pages>G823-G832</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><coden>APGPDF</coden><abstract>Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P<0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>19179625</pmid><doi>10.1152/ajpgi.90447.2008</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of physiology: Gastrointestinal and liver physiology, 2009-04, Vol.296 (4), p.G823-G832 |
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| source | American Physiological Society Journals |
| subjects | Alprostadil - administration & dosage Alprostadil - analogs & derivatives Alprostadil - pharmacology Animals Biochemistry Biological Transport - drug effects Cathartics - pharmacology Chlorides - metabolism Colon Colon - drug effects Colon - metabolism Dose-Response Relationship, Drug Guinea Pigs Histamine - metabolism Intestinal Mucosa - drug effects Intestinal Mucosa - metabolism Intestine, Small - drug effects Intestine, Small - metabolism Lubiprostone Mammals Membranes Mucosal Biology Neurons Neurons - physiology Prostaglandins - metabolism Small intestine |
| title | Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon |
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