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4. Inhibitory effect of salvinorin A, from Salvia divinorum, on ileitis-induced hypermotility: cross-talk between kappa-opioid and cannabinoid CB(1) receptors.

Author

Capasso, R., Borrelli, F., Cascio, M. G., Aviello, G., Huben, K., Zjawiony, J. K., Marini, P., Romano, B., Di Marzo, V., Capasso, F., and Izzo, A. A.

Subjects
SALVINORIN A, SALVIA divinorum, ILEITIS, CANNABINOIDS, INFLAMMATORY bowel diseases, HALLUCINOGENIC drugs, AMIDASES, ANIMAL experimentation, CELL physiology, CELL receptors, COMPARATIVE studies, ELECTRIC stimulation, GASTROINTESTINAL motility, HYDROCARBONS, SMALL intestine, LEAVES, RESEARCH methodology, MEDICAL cooperation, MICE, PLANTS, PRIMATES, RESEARCH, EVALUATION research
Abstract

Background and Purpose: 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.Experimental Approach: 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.Key Results: 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.Conclusions and Implications: 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. [ABSTRACT FROM AUTHOR]

Published
2008
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5. Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol

Author

Pagano, E., Montanaro, V., Di Girolamo, A., Pistone, A., Altieri, V., Zjawiony, J. K., Izzo, A. A., Raffaele Capasso, Pagano, Ester, Montanaro, V, Di Girolamo, A, Pistone, Antonio, Altieri, V, Zjawiony, Jk, Izzo, ANGELO ANTONIO, and Capasso, Raffaele

Subjects
Male, Mice, Cannabinoids, Plant Extracts, Urinary Bladder, Animals, Humans, Cannabis, Muscle Contraction
Abstract

There are anecdotal reports that some Cannabis preparations may be useful for bladder dysfunctions. Here, we investigated the effect of a number of non- psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabichromene (CBC) on mouse bladder contractility in vitro. CBG, THCV, CBD and CBDV, but not CBC, at concentration ranging from 10(-8) M to 10(-4) M, decreased (with similar potency), the contractions induced by acetylcholine without significantly modifying the contractions induced by electrical stimulation. The rank order of efficacy was CBG=THCVCBDCBDV. In depth studies on CBG showed that the effect of this phytocannabinoid on acetylcholine-induced contractions was not affected by CB1 or CB2 receptor antagonists. Additionally, CBG also reduced acetylcholine-induced contractions in the human bladder.

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