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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors.

K Taniyama, S Nakayama, K Takeda, S Matsuyama, J Shirakawa, I Sano and C Tanaka
Journal of Pharmacology and Experimental Therapeutics September 1991, 258 (3) 1098-1104;
K Taniyama
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S Nakayama
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K Takeda
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S Matsuyama
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J Shirakawa
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I Sano
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C Tanaka
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Abstract

The effects of cisapride on intestinal contractility and on release of acetylcholine (ACh) were examined using the longitudinal muscle with the myenteric plexus preparation from the guinea pig ileum, as related to the 5-hydoxytryptamine (5-HT) receptor. 5-HT exerted a dual effect, transient increase in ACh release (EC50 = 2 X 10(-6)M) via the 5-HT3 receptor, followed by inhibition (EC50 = 5 X 10(-9)M) via the 5-HT1 receptor. Cisapride at low concentrations (10(-9)M to 10(-8)M) enhanced electrical stimulation -evoked contraction and ACh release. The effect of cisapride was mimicked by methysergide and was not altered by ICS 205-930. Cisapride antagonized the 5-HT (5 X 10(-9) M)-induced inhibitory effect and the IC50 of cisapride was 1.5 X 10(-9) M. These findings indicate that enhancement by low concentrations of cisapride may be due to a block of the inhibitory 5-HT1 receptor. Cisapride at medium concentrations (10(-8) M to 3 X 10(-7) M) induced enhancement of electrical stimulation-evoked twitch contractions and ACh release evoked by electrical stimulation which were antagonized by 10(-6) M ICS 205-930, while this compound antagonized the 5-HT (2 X 10(-6) M)-and 2-methyl-5-HT-induced excitatory effects, and the IC50 of cisapride was 5.2 X 10(-8) M. Thus, cisapride acts on the putative 5-HT4 receptor as an agonist and the 5-HT3 receptor as an antagonist. Cisapride at high concentrations (10(-6) M to 10(-5) M) evoked contraction and the release of ACh, and these effects were antagonized by ICS 205-930 (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 258, Issue 3
1 Sep 1991
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Abstract

Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors.

K Taniyama, S Nakayama, K Takeda, S Matsuyama, J Shirakawa, I Sano and C Tanaka
Journal of Pharmacology and Experimental Therapeutics September 1, 1991, 258 (3) 1098-1104;

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Abstract

Cisapride stimulates motility of the intestine via the 5-hydroxytryptamine receptors.

K Taniyama, S Nakayama, K Takeda, S Matsuyama, J Shirakawa, I Sano and C Tanaka
Journal of Pharmacology and Experimental Therapeutics September 1, 1991, 258 (3) 1098-1104;
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