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10.1111/bph.13114 http://scihub22266oqcxt.onion/10.1111/bph.13114 C4459026!4459026!25684407     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Pharmacol 2015 ; 172 (12): 3099-111 Nephropedia Template TP {{tp|p=25684407|t=2015. Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation |pdf=|usr=}}{{25684407}} gab.com Text Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25684407 #FOAvip Background and Purpose: Endocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase-? (DAGL?), which is involved in biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Experimental Approach: Cannabinoid CB1 receptor-deficient, wild-type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGL? in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM-188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry. Key Results: DAGL? was expressed throughout the GI tract. In the intestine, unlike DAGL?, DAGL? immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2-AG was elevated while inhibiting DAGL normalized 2-AG levels. Conclusions and Implications: DAGL? was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2-AG and CB1 receptor-mediated mechanisms. Our data suggest that DAGL? inhibitors may be promising candidates for the treatment of constipation. Twit Text FOAVip Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=25684407 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25684407 #FOAvip English Wikipedia <ref>{{Cite pmid|25684407}}</ref> Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation #MMPMID25684407 Bashashati M; Nasser Y; Keenan CM; Ho W; Piscitelli F; Nalli M; Mackie K; Storr MA; Di Marzo V; Sharkey KA Br J Pharmacol 2015[Jun]; 172 (12): 3099-111 PMID25684407show ga Background and Purpose: Endocannabinoids are a family of lipid mediators involved in the regulation of gastrointestinal (GI) motility. The expression, localization and function of their biosynthetic enzymes in the GI tract are not well understood. Here, we examined the expression, localization and function of the enzyme diacylglycerol lipase-? (DAGL?), which is involved in biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Experimental Approach: Cannabinoid CB1 receptor-deficient, wild-type control and C3H/HeJ mice, a genetically constipated strain, were used. The distribution of DAGL? in the enteric nervous system was examined by immunohistochemistry. Effects of the DAGL inhibitors, orlistat and OMDM-188 on pharmacologically induced GI hypomotility were assessed by measuring intestinal contractility in vitro and whole gut transit or faecal output in vivo. Endocannabinoid levels were measured by mass spectrometry. Key Results: DAGL? was expressed throughout the GI tract. In the intestine, unlike DAGL?, DAGL? immunoreactivity was prominently expressed in the enteric nervous system. In the myenteric plexus, it was colocalized with the vesicular acetylcholine transporter in cholinergic nerves. In normal mice, inhibiting DAGL reversed both pharmacologically reduced intestinal contractility and pharmacologically prolonged whole gut transit. Moreover, inhibiting DAGL normalized faecal output in constipated C3H/HeJ mice. In colons incubated with scopolamine, 2-AG was elevated while inhibiting DAGL normalized 2-AG levels. Conclusions and Implications: DAGL? was expressed in the enteric nervous system of mice and its inhibition reversed slowed GI motility, intestinal contractility and constipation through 2-AG and CB1 receptor-mediated mechanisms. Our data suggest that DAGL? inhibitors may be promising candidates for the treatment of constipation. äInhibiting endocannabinoid biosynthesis: a novel approach to the treat(epmc).pdf DeepDyve Pubget Overpricing