Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors
| Autor: | Capasso R, Borrelli F, Cascio MG, Aviello G, Huben K, Zjawiony JK, Marini P, Romano B, Di Marzo V, Capasso F, Izzo AA. |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Mice Inbred ICR Croton Oil Receptors Opioid kappa Receptor Cross-Talk Ileitis Research Papers Electric Stimulation Amidohydrolases Diterpenes Clerodane Plant Leaves Receptor Cannabinoid CB2 Mice Receptor Cannabinoid CB1 COS Cells Chlorocebus aethiops Intestine Small Animals Salvia Gastrointestinal Motility Protein Binding |
| Zdroj: | British journal of pharmacology 155 (2008): 681–689. info:cnr-pdr/source/autori:Capasso R, Borrelli F, Cascio MG, Aviello G, Huben K, Zjawiony JK, Marini P, Romano B, Di Marzo V, Capasso F, Izzo AA./titolo:Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors/doi:/rivista:British journal of pharmacology/anno:2008/pagina_da:681/pagina_a:689/intervallo_pagine:681–689/volume:155 |
| ISSN: | 1476-5381 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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