Concentration-dependent actions of a new indene derivative, TN-871, in the enteric nervous system.
Intracellular electrical recordings and fluorimetric measurement of intracellular Ca2+ concentration ([Ca2+]i) were made from enteric neurons of the guinea-pig myenteric and submucosal plexuses to examine the actions of 2-n-butyl-1-(4-methylpiperazinyl)5,6-ethylendioxyindene x 2HCl (TN-871) on neural activity in the single cell. TN-871 affected neuronal electrophysiological properties and synaptic transmission in the enteric nervous system in a concentration-dependent manner; TN-871 at lower concentrations hyperpolarized enteric neurons and/or facilitated synaptic transmission, whereas at higher concentrations it depolarized enteric neurons and/or inhibited synaptic transmission. Experiments with fura-2 showed that TN-871 modulated both resting [Ca2+]i and [Ca2+]i-transient associated with action potentials. Thus, the present results demonstrated that TN-871 at lower concentrations facilitates but at higher concentrations depresses Ca2+-dependent or Ca2+-involving processes, suggesting that TN-871 may affect the Ca2+ dynamics in enteric neurons either directly, indirectly or both.
Katayama
Y
Y
Department of Autonomic Physiology, Medical Research Institute, Tokyo Medical and Dental University, Chiyodaku, Japan.
Morita
K
K
Hirai
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007192:Indenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D009435:Synaptic Transmission / Q000187:drug effects
C092715:2-n-butyl-1-(4-methylpiperazinyl)-5,6-methylenedioxyindene; D015220:Calcium Channels; D007192:Indenes