Z-338, a Newly Synthetized Carboxyamide Derivative, Stimulates Gastric Motility Through Enhancing the Excitatory Neurotransmission

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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 gastrointestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338(>10^<-8>M)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^<-8>M), a muscarinic M_1-antagonist, enhanced the EJP amplitude, although AF-DX116(M_2-)and 4-DAMP(M_3-antagonists)reduced the EJP amplitude, dose-dependently. The EC_<50> of the Z-338 and pirenzepine concentration response curves on EJPs were 4.7×10^<-8>M and 1.0×10^<-8>M, 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 neuroeffector transmission with no effect on NANC inhibitoty neuro-effector transmission in the guinea-pig stomach.
日本平滑筋学会の論文