gingerol and capsazepine

[6]-Gingerol possesses various beneficial pharmacological and therapeutic properties, including anti-carcinogenic and anti-inflammatory properties and the ability to regulate intestinal contraction. Recently, our group observed that the serosal administration of [6]-gingerol stimulated electrogenic sodium absorption in the rat colon via the capsaicin receptor, TRPV1. TRPV1 is known to be expressed in both the mucosal epithelium and the muscle layers in the colon. In the present study, we assessed whether [6]-gingerol stimulated sodium absorption via TRPV1 in the colonic mucosal epithelium. We compared the effect of [6]-gingerol on TRPV1-dependent colonic sodium absorption in the colon preparation with or without muscle layer. All experiments were performed by measuring the transmural potential difference (ΔPD) in an Ussing chamber system. [6]-Gingerol induced positive ΔPD when administered to the serosal side of the colon, and this effect was significantly larger in the colon preparation without muscle layer than in that with the muscle layer. In the colon preparation without muscle layer, the [6]-gingerol-dependent induction of ΔPD was markedly suppressed by mucosal addition of amiloride, a selective inhibitor of epithelial sodium channel. ΔPD induction by [6]-gingerol was considerably diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1, but not by AP-18, an inhibitor of TRPA1. These results suggest that [6]-gingerol induces amiloride-sensitive electrogenic sodium absorption in the rat colon via TRPV1 expressed in the colonic mucosal epithelium, and that this effect is independent of TRPV1 in the colonic muscle layer.

Topics: Amiloride; Animals; Capsaicin; Catechols; Colon; Epithelial Sodium Channel Blockers; Fatty Alcohols; Gastrointestinal Agents; In Vitro Techniques; Intestinal Absorption; Intestinal Mucosa; Membrane Potentials; Membrane Transport Modulators; Muscle, Smooth; Oximes; Rats, Sprague-Dawley; Sodium, Dietary; TRPA1 Cation Channel; TRPV Cation Channels

[6]-Gingerol possesses a variety of beneficial pharmacological and therapeutic properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic activities. Although [6]-gingerol is known to regulate the contraction of the intestine, its effect on intestinal ion transport is unclear. The aim of this study was to examine the role of [6]-gingerol in the regulation of electrogenic ion transport in the rat intestine by measuring the transmural potential difference (ΔPD). [6]-Gingerol induced significant positive ΔPD when administered to the serosal but not mucosal side of the colon, ileum, and jejunum; the highest effect was detected in the colon at a concentration of 10 μM. [6]-Gingerol-induced increase in ΔPD was suppressed by ouabain, an inhibitor of Na(+)/K(+)-ATPase, whereas no effect was observed in response to bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter. In addition, ΔPD induction by [6]-gingerol was greatly diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1. These results suggest that [6]-gingerol induced the electrogenic absorption of sodium in the rat colon via TRPV1.

Topics: Animals; Bumetanide; Capsaicin; Catechols; Colon; Enzyme Inhibitors; Fatty Alcohols; Ileum; Male; Membrane Potentials; Ouabain; Rats; Rats, Sprague-Dawley; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Exchanging ATPase; TRPV Cation Channels

1. Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists of the capsaicin-activated VR1 (vanilloid) receptor. 2. [6]-Gingerol and [8]-gingerol evoked capsaicin-like intracellular Ca(2+) transients and ion currents in cultured DRG neurones. These effects of gingerols were blocked by capsazepine, the VR1 receptor antagonist. 3. The potency of gingerols increased with increasing size of the side chain and with the overall hydrophobicity in the series. 4. We conclude that gingerols represent a novel class of naturally occurring VR1 receptor agonists that may contribute to the medicinal properties of ginger, which have been known for centuries. The gingerol structure may be used as a template for the development of drugs acting as moderately potent activators of the VR1 receptor.

Topics: Animals; Animals, Newborn; Calcium; Capsaicin; Catechols; Cells, Cultured; Dose-Response Relationship, Drug; Fatty Alcohols; Fura-2; Ganglia, Spinal; Membrane Potentials; Neurons; Rats; Receptors, Drug; Time Factors