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Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating κ‐opioid and cannabinoid receptors
Author(s) -
Fichna J.,
Schicho R.,
Andrews C. N.,
Bashashati M.,
Klompus M.,
Mckay D. M.,
Sharkey K. A.,
Zjawiony J. K.,
Janecka A.,
Storr M. A.
Publication year - 2009
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2009.01369.x
Subject(s) - pharmacology , cannabinoid , in vivo , cannabinoid receptor agonists , cannabinoid receptor type 2 , chemistry , opioid , motility , receptor , dynorphin , cannabinoid receptor , veratridine , ussing chamber , medicine , in vitro , biology , biochemistry , opioid peptide , agonist , microbiology and biotechnology , sodium , sodium channel , organic chemistry
The major active ingredient of the plant Salvia divinorum , salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo . The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro , prolonged colonic propulsion and slowed upper GI transit in vivo . Salvinorin A had no effect on gastric emptying in vivo . Salvinorin A reduced veratridine‐, but not forskolin‐induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by κ‐opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor‐binaltorphimine (KOR), AM 251 (CB 1 receptor) and AM 630 (CB 2 receptor). However, in the colon in vivo , the effects were largely mediated by KORs. The effects of SA on veratridine‐mediated epithelial ion transport were inhibited by nor‐binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.