Characterization of Two Models of Drug-Induced Constipation in Mice and Evaluation of Mustard Oil in These Models

Abstract

Although it is known that both clonidine and loperamide cause delayed colonic transit in mice, these models of drug-induced experimental constipation have not yet been fully characterized. Therefore, the aims of this study were to validate the clonidine- and loperamide-induced delays of colonic transit in mice as models of atonic and spastic constipation, respectively, and to evaluate the effect of mustard oil, a TRPA1 agonist, in both models. Colonic transit was evaluated in mice by determining the time needed to evacuate a bead inserted into the distal colon. Both loperamide and clonidine dose-dependently prolonged the evacuation time. Clonidine (10 μg/kg) and loperamide (0.3 mg/kg) tripled the evacuation time compared to controls. These delays were antagonized by the administration of yohimbine and naloxone, respectively. Tegaserod, a gastrointestinal motor-stimulating drug, reversed the delay in both models, but the effects were diminished at high doses. Atropine, an antispastic drug, improved the loperamide-induced delay, but did not affect the clonidine-induced delay. Mustard oil accelerated the colonic transit dose-dependently in both models of drug-induced constipations. These results indicate that clonidine- and loperamide-induced delays in colonic transit are models of atonic and spastic constipation, respectively, and that mustard oil may be effective on both types of constipation.

Effects of Allyl Isothiocyanate, Acetaminophen, and Dipyrone in the Guinea-Pig Ileum

“…The rather complex mode of action of AITC observed in this study, with a variable initial contractile response followed by a reproducible inhibitory effect on the twitch, and variable effects on the basal tone, has been found to fit the complex mechanisms of action reported so far [4][5][6][7][8][9]15] . Excitatory effects for AITC have been reported in whole segments of the guinea-pig ileum, in the mouse colon, and in human jejunal strips [1,[4][5][6]15] .…”

“…Excitatory effects for AITC have been reported in whole segments of the guinea-pig ileum, in the mouse colon, and in human jejunal strips [1,[4][5][6]15] . Inhibitory effects on stimulation-induced contractions have been reported for the mouse ileum and in in vivo experiments on gastric emptying and drug-induced constipation [1,6,9] . As the most important finding, the present investigation provides evidence for a spasmolytic type of action of AITC (mustard oil) in the electrically driven guinea pig LMMP strip ( fig.…”

Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

“…Furthermore, a subtype of enteroendocrine cells has been shown to express abundant TRPA1 whose stimulation induces 5-HT release that can activate intrinsic nerves and vagal endings (39). These reports strongly suggest that TRPA1 may play a role in the regulation of gut motility as confirmed by several motility studies of experimental animals using TRPA1 ligands and gene-manipulation (11,12,26,42,43). More recently, considerable attention has been given to the presence of TRPA1 in IE cells.…”

Effect of CB1 Ligands on Neurogenic and Myogenic Contractile Responses in the Guinea-Pig Ileum

“…AITC is known to exert initial stimulatory effects of its own and consequently neurogenic as well as myogenic inhibitory effects on isolated intestinal smooth muscle strips [14,[16][17][18][19][20]. AITC, at a concentration of 100 µmol/L, evokes TRPA1 receptor-mediated effects as well as receptor-independent or unspecific effects in in vitro experiments in organ bath studies, with a spasmolytic type of action [14, 16-20, 26, 27].…”

“…In this context, an interaction of cannabinoids with other myorelaxant constituents of food and food supplements in the gastrointestinal tract is of general interest. Allyl isothiocyanate (AITC, mustard oil) is consumed as a constituent of vegetables, and AITC exerts stimulatory effects on its own and neurogenic as well as myogenic inhibitory effects on isolated intestinal smooth muscle strips [14,[16][17][18][19][20]. Therefore, we searched for an additive antispasmodic effect of cannabinoid CB1 agonists and AITC.…”