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The endocannabinoid system and the molecular basis of paralytic ileus in mice
Author(s) -
Mascolo Nicola,
Izzo Angelo A.,
Ligresti Alessia,
Costagliola Anna,
Pinto Luisa,
Cascio Maria G.,
Maffia Pasquale,
Cecio Aldo,
Capasso Francesco,
Marzo Vincenzo
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0338fje
Subject(s) - anandamide , endocannabinoid system , cannabinoid receptor , cannabinoid , pharmacology , chemistry , receptor , medicine , ileus , endocrinology , antagonist
The endocannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) plays an important role in the physiological control of intestinal motility. However, its participation in intestinal pathological states is still poorly understood. In the present study, we investigated the possible role of the endocannabinoid system in the pathogenesis of paralytic ileus, a pathological state consisting of decreased intestinal motility following peritonitis, surgery, or other noxious situations. Ileus was induced by i.p. administration of acetic acid, and gastrointestinal propulsion was assessed by the charcoal method. Endocannabinoid levels were measured by isotope‐dilution gas chromatography‐mass spectrometry, whereas cannabinoid CB 1 receptors were identified by immunohistochemistry. Acetic acid administration inhibited gastrointestinal transit (ileus), and this effect was accompanied by increased levels of the endocannabinoid anandamide compared with control mice and by overexpression of CB 1 receptors in myenteric nerves. Furthermore, acetic acid‐induced ileus was alleviated by the CB 1 receptor antagonist SR141716A and worsened by VDM11, a selective inhibitor of anandamide cellular uptake (and hence inactivation). From these findings, it can be concluded that the intestinal hypomotility typical of paralytic ileus is due, at least in part, to the enhancement of anandamide levels and CB 1 expression during this condition, and that selective, nonpsychotropic CB 1 receptor antagonists could represent new drugs to treat this disorder.