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 CB1 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 CB1 receptors in myenteric nerves. Furthermore, acetic acid-induced ileus was alleviated by the CB1 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 CB1 expression during this condition, and that selective, nonpsychotropic CB1 receptor antagonists could represent new drugs to treat this disorder.
The presence and distribution of nicotinamide dinucleotide phosphate diaphorase (NADPH-d)-containing neurons have been studied by means of NADPH-d histochemistry in different regions of the adult cow gut, from the esophagus to the rectum. NADPH-d and nitric oxide synthase (NOS) were constantly recognized to be colocalized in the same neuron. The colocalization of vasoactive intestinal polypeptide (VIP) and galanin in such nitrergic neurons was also studied by means of combined histochemical and immunofluorescence techniques. NADPH-d-positive neurons were present along the myenteric plexus of the entire gut, and in the submucous plexus from the abomasum to the rectum. Notably, they formed two types of nerve networks in the submucous connective tissue of the jejunum-ileum. NADPH-d-positive innervation of the muscle layers occurred throughout the tract, and sometimes a clear correspondence was noted between the number of reactive fibres and the thickness of the muscle. Nitrergic fibres also occurred in the mucosa and often were in relation to glands and blood vessels. The nitrergic neurons varied in size, shape, and intensity of staining, and often their terminals were seen to surround unstained perikarya. Various types of neurons were recognized on the basis of their chemical content; one of them contained galanin, VIP and NOS simultaneously. The present results suggest that the nitrergic neurons of the bovine gastrointestinal tract play roles presumably for controlling the motility of the gut and the conduction of interneuronal impulses.
A systematic search for neuroendocrine (NE) cells in the urogenital organs of the pig was carried out by means of Linder’s argyrophil method and immunohistochemical techniques. The occurrence, distribution and immunohistochemical character of NE cells (paraneurons) were studied in the vaginal vestibulum, vagina, uterus, oviduct, ovary, urethra, urinary bladder and ureter. In the vestibular glands paraneurons were found to be the most numerous, while a moderate number of these cells occurred in the uterine horn and in the urethra. A distinctly smaller number of paraneurons was present in the oviduct and only occasional NE cells were observed in the urinary bladder. Immunohistochernistry was performed by using the peroxidase-antiperoxidase procedure. Different subpopulations of paraneurons were distinguishable. Chromogranin A-positive paraneurons were found in the vestibular glands, uterine horns, oviducts, urethra and urinary bladder. Somatostatin positivity was observed in NE cells of the vestibular gland, uterine horn, oviduct and urethra. The subpopulation of serotonin-positive paraneurons was present in the vestibular gland and urethra. Bombesin, vasoactive intestinal polypeptide, cholecystokinin, substance P, nitric oxide synthase, β-endorphin, insulin, adrenocorticotropic hormone, oxytocin and thyroid-stimulating hormone antibodies gave negative reactions in the studied NE cells.
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