Concentration-dependent actions of a new indene derivative, TN-871, in the enteric nervous system

European Journal of Pharmacology
Y KatayamaK Hirai

Abstract

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.

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