Z-338, a newly synthetized carboxyamide derivative, stimulates gastric motility through enhancing the excitatory neurotransmission.
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 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 x 10(-8) M and 1.0 x 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 neuro effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.
Nakajima
T
T
Department of Pharmacology and Bioregulatory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nawata
H
H
Ito
Y
Y
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D013270:Stomach / Q000294:innervation / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*
D001549:Benzamides; D005765:Gastrointestinal Agents; D013844:Thiazoles; C410959:Z 338