Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.
Raffaele Capasso, Francesca Borrelli, M G Cascio, Gabriella Aviello, Krzysztof Huben, Jordan K Zjawiony, P Marini, Barbara Romano, V Di Marzo, F Capasso, Angelo A Izzo
British Journal of Pharmacology November 1, 2008 DOI: 10.1038/bjp.2008.294 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Salvinorin A U-50488 nor-binaltorphimine rimonabant croton oil |
| Topics | Salvia divinorum |
| Keywords | Natural compound Gastrointestinal health Gut health Gut motility Ileitis Digestive system Receptor pharmacology Kappa-opioid receptors Cannabinoid cb1 receptors Receptor systems Mechanism of action Anti-inflammatory Calming gut Reducing inflammation Gut discomfort management Therapeutic potential |
| Citations | 82 |
| Key findings | Salvinorin A reduces intestinal motility in inflamed gut through a functional interaction between kappa-opioid receptors and cannabinoid CB1 receptors, an effect not seen in healthy gut. |
Abstract
Salvinorin A, the active component of the hallucinogenic herb Salvia divinorum, inhibits intestinal motility through activation of kappa-opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A-induced delay in motility in the inflamed gut. Motility in vivo was measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays. Salvinorin A as well as the KOR agonist U-50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U-50488 was counteracted by the KOR antagonist nor-binaltorphimine and by the cannabinoid CB(1) receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB(1) and CB(2) and no inhibitory effect on 2-arachidonoylglycerol and anandamide hydrolysis and cellular uptake. The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB(1) receptors and KORs in the inflamed--but not in the normal--gut in vivo.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 18
- Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents British Journal of Pharmacology May 5, 2009
- Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo. Journal of Molecular Medicine September 1, 2011
- Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid. Journal of Pharmacology and Experimental Therapeutics February 1, 2009
- From local to global-fifty years of research on Salvia divinorum. Journal of Ethnopharmacology February 3, 2014
- Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents. Psychopharmacology June 1, 2010
and 13 more in the library
Cites 19
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum(Labiatae) Journal of the Chemical Society Perkin Transactions 1 1982
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Psychopharmacology May 1, 2005
- Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum The Journal of Organic Chemistry November 1, 1984
and 14 more in the library