Endocannabinoids as physiological regulators of colonic propulsion in mice
Background & Aims: Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investi...
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description | Background & Aims: Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo. Methods: Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography–mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry. Results: Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus. Conclusions: We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.
GASTROENTEROLOGY 2002;123:227-234 |
doi_str_mv | 10.1053/gast.2002.34242 |
format | Article |
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GASTROENTEROLOGY 2002;123:227-234</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/gast.2002.34242</identifier><identifier>PMID: 12105851</identifier><identifier>CODEN: GASTAB</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Amidohydrolases - metabolism ; Animals ; Arachidonic Acids - pharmacology ; Biological and medical sciences ; Cannabinoid Receptor Modulators ; Cannabinoids - metabolism ; Colon - physiology ; Digestive system ; Endocannabinoids ; Ethanolamines ; Gastrointestinal Motility - drug effects ; Gastrointestinal Motility - physiology ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Mice ; Mice, Inbred ICR ; Palmitic Acids - metabolism ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Receptors, Cannabinoid ; Receptors, Drug - agonists ; Receptors, Drug - antagonists & inhibitors</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2002-07, Vol.123 (1), p.227-234</ispartof><rights>2002 American Gastroenterological Association</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-f8db23d716ee937f2f0629519af2095fbda139cda2e1b0c5fa1c5a85ee5913ec3</citedby><cites>FETCH-LOGICAL-c373t-f8db23d716ee937f2f0629519af2095fbda139cda2e1b0c5fa1c5a85ee5913ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0016508502000823$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13768201$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12105851$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pinto, Luisa</creatorcontrib><creatorcontrib>Izzo, Angelo A.</creatorcontrib><creatorcontrib>Mascolo, Nicola</creatorcontrib><creatorcontrib>Capasso, Francesco</creatorcontrib><creatorcontrib>Cascio, Maria Grazia</creatorcontrib><creatorcontrib>Bisogno, Tiziana</creatorcontrib><creatorcontrib>Di Marzo, Vincenzo</creatorcontrib><creatorcontrib>Hospodar–Scott, Karen</creatorcontrib><creatorcontrib>Brown, David R.</creatorcontrib><title>Endocannabinoids as physiological regulators of colonic propulsion in mice</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Background & Aims: Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo. Methods: Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography–mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry. Results: Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus. Conclusions: We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.
GASTROENTEROLOGY 2002;123:227-234</description><subject>Amidohydrolases - metabolism</subject><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cannabinoid Receptor Modulators</subject><subject>Cannabinoids - metabolism</subject><subject>Colon - physiology</subject><subject>Digestive system</subject><subject>Endocannabinoids</subject><subject>Ethanolamines</subject><subject>Gastrointestinal Motility - drug effects</subject><subject>Gastrointestinal Motility - physiology</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Palmitic Acids - metabolism</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Receptors, Cannabinoid</subject><subject>Receptors, Drug - agonists</subject><subject>Receptors, Drug - antagonists & inhibitors</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFPGzEQhS1URFLg3BvaS7ltGNvx7vqIUIBWkXqBs-W1x8FoYwd7t1L-PU4TiVNPTxp972n0EfKDwoKC4HcbnccFA2ALvmRLdkbmVLCuBqDsG5mXaGoBnZiR7zm_A4DkHb0gM8pKuxN0Tn6vgo1Gh6B7H6K3udK52r3ts49D3HijhyrhZhr0GFOuoqtMuQdvql2Ku2koWKh8qLbe4BU5d3rIeH3KS_L6uHp5eK7Xf55-Pdyva8NbPtausz3jtqUNouStYw4aJgWV2jGQwvVWUy6N1QxpD0Y4TY3QnUAUknI0_JLcHnfLCx8T5lFtfTY4DDpgnLJqaScBlk0B746gSTHnhE7tkt_qtFcU1EGfOuhTB33qn77SuDlNT_0W7Rd_8lWAnydA5-LGJR2Mz18cb5uOwYGTRw6LiL8ek8rGYzBofUIzKhv9f5_4BBNajQ4</recordid><startdate>20020701</startdate><enddate>20020701</enddate><creator>Pinto, Luisa</creator><creator>Izzo, Angelo A.</creator><creator>Mascolo, Nicola</creator><creator>Capasso, Francesco</creator><creator>Cascio, Maria Grazia</creator><creator>Bisogno, Tiziana</creator><creator>Di Marzo, Vincenzo</creator><creator>Hospodar–Scott, Karen</creator><creator>Brown, David R.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20020701</creationdate><title>Endocannabinoids as physiological regulators of colonic propulsion in mice</title><author>Pinto, Luisa ; Izzo, Angelo A. ; Mascolo, Nicola ; Capasso, Francesco ; Cascio, Maria Grazia ; Bisogno, Tiziana ; Di Marzo, Vincenzo ; Hospodar–Scott, Karen ; Brown, David R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-f8db23d716ee937f2f0629519af2095fbda139cda2e1b0c5fa1c5a85ee5913ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amidohydrolases - metabolism</topic><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cannabinoid Receptor Modulators</topic><topic>Cannabinoids - metabolism</topic><topic>Colon - physiology</topic><topic>Digestive system</topic><topic>Endocannabinoids</topic><topic>Ethanolamines</topic><topic>Gastrointestinal Motility - drug effects</topic><topic>Gastrointestinal Motility - physiology</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Palmitic Acids - metabolism</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Receptors, Cannabinoid</topic><topic>Receptors, Drug - agonists</topic><topic>Receptors, Drug - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pinto, Luisa</creatorcontrib><creatorcontrib>Izzo, Angelo A.</creatorcontrib><creatorcontrib>Mascolo, Nicola</creatorcontrib><creatorcontrib>Capasso, Francesco</creatorcontrib><creatorcontrib>Cascio, Maria Grazia</creatorcontrib><creatorcontrib>Bisogno, Tiziana</creatorcontrib><creatorcontrib>Di Marzo, Vincenzo</creatorcontrib><creatorcontrib>Hospodar–Scott, Karen</creatorcontrib><creatorcontrib>Brown, David R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pinto, Luisa</au><au>Izzo, Angelo A.</au><au>Mascolo, Nicola</au><au>Capasso, Francesco</au><au>Cascio, Maria Grazia</au><au>Bisogno, Tiziana</au><au>Di Marzo, Vincenzo</au><au>Hospodar–Scott, Karen</au><au>Brown, David R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endocannabinoids as physiological regulators of colonic propulsion in mice</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>2002-07-01</date><risdate>2002</risdate><volume>123</volume><issue>1</issue><spage>227</spage><epage>234</epage><pages>227-234</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><coden>GASTAB</coden><abstract>Background & Aims: Activation of enteric cannabinoid CB1 receptors inhibits motility in the small intestine; however, it is not known whether endogenous cannabinoids (anandamide and 2-arachidonylglycerol) play a physiologic role in regulating intestinal motility. In the present study, we investigated the possible involvement of endocannabinoids in regulating intestinal propulsion in the mouse colon in vivo. Methods: Intestinal motility was studied measuring the expulsion of a glass bead inserted into the distal colon; endocannabinoid levels were measured by isotope-dilution gas chromatography–mass spectrometry; anandamide amidohydrolase activity was measured by specific enzyme assays. CB1 receptors were localized by immunohistochemistry. Results: Anandamide, WIN 55,212-2, cannabinol (nonselective cannabinoid agonists), and ACEA (a selective CB1 agonist) inhibited colonic propulsion; this effect was counteracted by SR141716A, a CB1 receptor antagonist. Administered alone, SR141716A increased motility, whereas the inhibitor of anandamide cellular reuptake, VDM11, decreased motility. High amounts of 2-arachidonylglycerol and particularly anandamide were found in the colon, together with a high activity of anandamide amidohydrolase. CB1 receptor immunoreactivity was colocalized to a subpopulation of choline acetyltransferase-immunoreactive neurons and fiber bundles in the myenteric plexus. Conclusions: We conclude that endocannabinoids acting on myenteric CB1 receptors tonically inhibit colonic propulsion in mice.
GASTROENTEROLOGY 2002;123:227-234</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>12105851</pmid><doi>10.1053/gast.2002.34242</doi><tpages>8</tpages></addata></record> |
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subjects | Amidohydrolases - metabolism Animals Arachidonic Acids - pharmacology Biological and medical sciences Cannabinoid Receptor Modulators Cannabinoids - metabolism Colon - physiology Digestive system Endocannabinoids Ethanolamines Gastrointestinal Motility - drug effects Gastrointestinal Motility - physiology Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Mice Mice, Inbred ICR Palmitic Acids - metabolism Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Receptors, Cannabinoid Receptors, Drug - agonists Receptors, Drug - antagonists & inhibitors |
title | Endocannabinoids as physiological regulators of colonic propulsion in mice |
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