Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.
R Capasso, F Borrelli, M G Cascio, G Aviello, K Huben, J K Zjawiony, P Marini, B Romano, V Di Marzo, F Capasso, A A Izzo
British journal of pharmacology November 1, 2008 DOI: 10.1038/bjp.2008.294 via PubMed
Summary
AI-generated from the abstractSalvinorin A, the active compound in Salvia divinorum, slows intestinal movement by activating kappa-opioid receptors (KORs). In mice with croton oil-induced intestinal inflammation, this effect also involves cannabinoid CB1 receptors, as the CB1 antagonist rimonabant blocked the motility delay. In healthy mice, rimonabant did not affect salvinorin A's action. Binding tests showed salvinorin A has very weak affinity for CB1 and CB2 receptors and does not inhibit endocannabinoid breakdown or uptake. The findings suggest a functional interaction between CB1 receptors and KORs occurs specifically in the inflamed gut, not in the normal gut.
Study at a glance
| 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 |
| Citations | 82 |
| Key finding | 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.