Anthraquinone stimulant cathartics such as emodin are believed to increase the rate of contraction of ileum tissue in vitro via multiple mechanisms including elevated Ca²⁺ concentrations (Cheng & Kang, 1998), releasing prostaglandins (Yagi et al., 1991), 5-hydroxytryptamine (Capasso et al., 1991) and tachykinins (Croci et al., 1997) as well as inhibiting nitric oxide synthase (Izzo et al., 1996). The aim of this study was to probe the effects of emodin on acetylcholine (ACh)-induced contraction of the rat isolated ileum preparation using the muscarinic agonist methacholine, ACh, the muscarinic antagonist atropine and the choline uptake inhibitor hemicholinium (HC-3).

Ileal segments (2 sections taken 15-30 cm from the ileo-caecal junction) were obtained from male Wistar rats (220 – 250g) and mounted in 10ml organ baths containing Tyrode’s solution at 35 ^oC, gassed with 95% O₂ : 5% CO₂, under a tension of 1g. Tissues were equilibrated for 20 min before non-cumulative dose response curves to ACh, methacholine and emodin were obtained using a 3 min cycle with 30s contact time using an isotonic transducer. Atropine (1 µM) was added to the buffer and tissues equilibrated for 20 min before retesting the effects of methacholine and emodin. HC-3 (1 µM & 10 µM) was added to the buffer and tissues equilibrated for 20 min before retesting the effects of ACh and emodin. Depletion of endogenous ACh in the presence of HC-3 (1 µM & 10 µM) was achieved by construction of an ACh dose response curve, using exogenous ACh, prior to retesting the effects of emodin in the presence of HC-3. A dose of ACh (0.2 µM) was added in between each dose of emodin so as to ensure continued depletion of endogenous ACh. Data are mean ± s.e. and statistical significance was determined using Student’s t-test for pair differences.

Emodin (5 µM – 1 mM) caused dose-dependent tissue contraction with an EC₅₀ value of 42 ± 8 µM (n = 6). Inclusion of atropine (1 µM) in the buffer abolished the contractile effects of emodin and reduced the maximum response caused by methacholine to 54 ± 11% (P<0.001, n = 6). Incubation of tissues with HC-3 (1 µM & 10 µM) reduced the maximum response caused by emodin by 45 ± 6% (n = 6; P<0.01) and 71 ± 6% (n = 6; P<0.001) respectively, but had no effect on ACh-induced tissue contraction.

These data suggest that, emodin triggers the release of endogenous ACh which acts on muscarinic receptors to cause contraction of the rat isolated ileum preparation. The mechanism by which emodin triggers the release of ACh remains to be determined.

Capasso, F. et al., (1991), J. Pharmaceutical Pharmacology, 43, 307-310
Cheng, Y.W. & Kang, J.J. (1998) Brit. J. Pharmacol. 123, 815-820
Croci, T. et al., (1997) Brit. J. Pharmacol. 121, 375-380
Izzo, A.A. et al., (1996), Eur. J. Pharmacol. 301, 137-142
Yagi, T. et al., (1991) J. Pharmaceutical Pharmacology, 43, 307-310