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Arecoline excites the contraction of distal colonic smooth muscle strips in rats via the M3 receptor - extracellular Ca2+ influx - Ca2+ store release pathway

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Areca is a Chinese herbal medicine that is widely used for constipation. However the mechanisms of its action are not clear. We investigated the effects of arecoline, the most active component of areca, on the motility of rat distal colonic smooth muscle strips. In longitudinal muscle of distal colon (LMDC) and circular muscle of distal colon (CMDC), arecoline increased the contraction in a dose-dependent manner. Tetrodotoxin (TTX) did not inhibit the effects of arecoline. The contractile response to arecoline was completely antagonized by atropine. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) strongly depressed the response to arecoline, but gallamine and methoctramine did not. Nifedipine, 2-aminoethoxydiphenyl borate (2-APB), and Ca2+-free Krebs solution with EGTA partly inhibited the effects of arecoline. The sum of Ca2+-free Krebs solution, EGTA, and 2-APB completely inhibited the effects of arecoline. The results show that arecoline stimulates distal colonic contraction in rats via the muscarinic (M3) receptor - extracellular Ca2+ influx - Ca2+ store release pathway. It is likely that the action of areca in relieving constipation is due to its stimulation of muscle contraction.

L’areca est une herbe médicinale chinoise abondamment utilisée pour traiter la constipation. Toutefois, on connaît peu ses mécanismes d’action. Nous avons examiné les effets de l’arécoline, le composant le plus actif de l’areca, sur la motilité de lambeaux de muscles lisses du côlon distal du rat. Dans le muscle longitudinal (MLCD) et le muscle circulaire (MCCD) du côlon distal, l’arécoline a augmenté la contraction en fonction de la dose utilisée. La tétrodotoxine (TTX) n’a pas inhibé les effets de l’arécoline. L’atropine a totalement antagonisé la réponse contractile à l’arécoline. Le 4-diphénylacétoxy-N-méthylpipéridine méthiodide (4-DAMP), contrairement à la gallamine et à la méthoctramine, a significativement diminué la réponse à l’arécoline. La nifédipine, le 2-aminoéthoxydiphényl borate (2-APB) et une solution de Krebs sans Ca2+ contenant d’EGTA ont partiellement inhibé les effets de l’arécoline. Ensemble, la solution de Krebs sans Ca2+, l’EGTA et le 2-APB ont totalement inhibé ses effets. Les résultats montrent que l’arécoline stimule la contraction du côlon distal chez les rats par la voie récepteurs M3 - influx de Ca2+ extracellulaire - libération des réserves de Ca2+. Il est probable que l’areca apporte un soulagement de la constipation en stimulant la contraction musculaire.
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Document Type: Research Article

Publication date: April 1, 2010

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