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

元データ 日本平滑筋学会


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.


NAWATA Hajime Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences
Nawata H Department Of Medicine And Bioregulatory Science Graduate School Of Medical Sciences Kyushu Universi
Nawata Hajime 九州大学 医研究院病態制御内科学
Nawata H Kyushu Univ. Fukuoka Jpn
Ito Yushi Graduate School Of Medical Sciences Kyushu University
Nawata Hajime Department Of Anesthesiology And Critical Care Medicine Kyushu University School Of Medicine
Nawata Hajime Department Of Medicine And Bioregulatory Science Graduate School Of Medical Science Kyushu Universit
Nawata H Kyushu Univ. Fukuoka
NAKAJIMA Tadasu Graduate School of Medical Sciences, Kyushu University
Nakajima Tadasu Graduate School Of Medical Sciences Kyushu University