Journal of Smooth Muscle Research
Online ISSN : 1884-8796
Print ISSN : 0916-8737
ISSN-L : 0916-8737
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Z-338, a Newly Synthetized Carboxyamide Derivative, Stimulates Gastric Motility Through Enhancing the Excitatory Neurotransmission
Tadasu NAKAJIMAHajime NAWATAYushi ITO
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JOURNAL FREE ACCESS

2000 Volume 36 Issue 2 Pages 69-81

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Abstract

We studied the effects of Z-338, a newly synthesized carboxyamide derivative, on autonomic neuroeffector transmission in the guinea-pig stomach in relation to its gastro-intestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338 (>10-8M) dose-dependently enhanced the amplitude of twitch-like contractions and excitatory junction potentials (EJPs) evoked by single or repetitive electrical field stimulation (EFS) without affecting the non-adrenergic non-cholinergic (NANC) relaxation and inhibitory junction potentials (IJPs) in the circular muscle strips of the guinea-pig stomach. Similar to the action of Z-338, pirenzepine (>10-8M), a muscarinic M1-antagonist, enhanced the EJP amplitude, although AF-DX116 (M2-) and 4-DAMP (M3-antagonists) reduced the EJP amplitude, dose-dependently. The EC50 of the Z-338 and pirenzepine concentration response curves on EJPS were 4.7×10-8 M and 1.0×10-8M, and Hill coefficients were 0.96 and 0.94 respectively. In addition, Z-338 slightly but significantly enhanced the amplitude of slow waves with or without initial spike. These results provide the first evidence that Z-338 exerts its gastrointestinal prokinetic action mainly through enhancing excitatory neuro-effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc/4.0/deed.ja
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