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

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Author(s)

    • NAKAJIMA Tadasu
    • Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University
    • NAWATA Hajime
    • Department of Bioregulatory Medicine, Graduate School of Medical Sciences, Kyushu University
    • ITO Yushi
    • Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University

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<SUP><FONT SIZE=-1>-8</FONT></SUP>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<SUP><FONT SIZE=-1>-8</FONT></SUP>M), a muscarinic M<SUB><FONT SIZE=-1>1</FONT></SUB>-antagonist, enhanced the EJP amplitude, although AF-DX116 (M<SUB><FONT SIZE=-1>2-</FONT></SUB>) and 4-DAMP (M<SUB><FONT SIZE=-1>3</FONT></SUB>-antagonists) reduced the EJP amplitude, dose-dependently. The EC<SUB><FONT SIZE=-1>50</FONT></SUB> of the Z-338 and pirenzepine concentration response curves on EJPS were 4.7×10<SUP><FONT SIZE=-1>-8</FONT></SUP> M and 1.0×10<SUP><FONT SIZE=-1>-8</FONT></SUP>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.

Journal

  • Journal of Smooth Muscle Research

    Journal of Smooth Muscle Research 36(2), 69-81, 2000-04-01

    Japan Society of Smooth Muscle Research

References:  22

Cited by:  2

Codes

  • NII Article ID (NAID)
    110002929808
  • NII NACSIS-CAT ID (NCID)
    AN10364204
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09168737
  • Data Source
    CJP  CJPref  NII-ELS  J-STAGE 
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