Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 877, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173087
Keywords
beta(1)-adrenergic; Cancer cachexia; Endocannabinoid; Gastrointestinal motility; Vagus nerve
Categories
Funding
- Office to Coordinate Improvement of Higher Education Personnel (CAPES)
- National Council for Scientific and Technological Development (CNPq)
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The aim of this study was to investigate the effect of cachexia induced by AH-130 cells on gastrointestinal motility in rats. We evaluated food intake, body weight variation, cachexia index, gastric emptying and in vitro gastric responsiveness of control or cachexia rats. In addition, we evaluated the effect of pretreatment with atenolol (20 mg/kg, p.o.), win 55,212-2 (2 mg/kg, s.c.) or subdiaphragmatic vagotomy on the effects found. Atenolol prevented (P < 0.05) the acceleration of gastric emptying (area under the curve, AUC, 20360.17 +/- 1970.9 vs. 12579.2 +/- 785.4 mu g/min/ml), and increased gastric responsiveness to carbachol (CCh) stimulation in cachectic rats compared to control groups (CCh-6M: 63.2 +/- 5.5% vs. 46.5 +/- 5.7%). Vagotomy prevented (P < 0.05) increase in gastric emptying acceleration (AUC 20360.17 +/- 1970.9 vs. 13414.0 +/- 1112.9 mu g/min/ml) and caused greater in vitro gastric responsiveness of cachectic compared to control rats (CCh-6M: 63.2 +/- 5.5% vs. 31.2 +/- 4.7%). Win 55,212-2 attenuated the cachexia index (38.5 +/- 2.1% vs. 25.8 +/- 2.7%), as well as significantly (P < 0.05) preventing increase in gastric emptying (AUC 20360.17 +/- 1970.9 vs. 10965.4 +/- 1392.3 mu g/min/ml) and gastric responsiveness compared to control groups (CCh-6M: 63.2 +/- 5.5% vs. 38.2 +/- 3.9%). Cachexia accelerated gastric emptying and increased gastric responsiveness in vitro. These phenomena were prevented by subdiaphragmatic vagotomy and by atenolol and win 55,212-2 treatments, showing vagal involvement of beta(1)-adrenergic and cannabinoid CB1/CB2 receptors.
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