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Modulation of Spontaneous and Stimulation‐Evoked Transmitter Release from Rat Sympathetic Neurons by the Cognition Enhancer Linopirdine: Insights into Its Mechanisms of Action
Author(s) -
Kristufek Doris,
Koth Gabriele,
Motejlek Andrea,
Schwarz Karin,
Huck Sigismund,
Boehm Stefan
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722083.x
Subject(s) - neuroscience , stimulation , enhancer , action (physics) , chemistry , biology , physics , transcription factor , biochemistry , quantum mechanics , gene
The mechanisms by which the cognition enhancer linopirdine may affect transmitter release were investigated in cultures of rat superior cervical ganglion neurons. Overflow of previously incorporated [ 3 H]noradrenaline evoked by 10 μ M UTP or 0.1 μ M bradykinin was enhanced by linopirdine at ∼3 μ M , overflow evoked by 25 m M K + , 100 μ M nicotine, or 300 μ M ATP was enhanced by linopirdine at ∼10 μ M , and overflow due to 40 m M K + or electrical field stimulation was not altered by linopirdine. Ba 2+ (0.3 m M ) augmented the same types of stimulation‐evoked overflow to a similar extent as linopirdine. K + (25 m M ), nicotine (100 μ M ), and ATP (300 μ M ) triggered transmitter release in a partially tetrodotoxin‐resistant manner, and the release‐enhancing action of linopirdine was lost in the presence of tetrodotoxin (1 μ M ). Linopirdine (10 μ M ) raised spontaneous tritium outflow and reduced currents through muscarinic K + (K M ) channels with a similar time course. The secretagogue action of linopirdine was concentration‐ and Ca 2+ ‐dependent and abolished by tetrodotoxin (1 μ M ) or Cd 2+ (100 μ M ). Linopirdine (10 μ M ) added to the partial inhibition of K M channels by 1 or 3 m M Ba 2+ but not to the complete inhibition by 10 m M Ba 2+ . Likewise, the secretagogue action of 1 and 3 m M , but not that of 10 m M , Ba 2+ was enhanced by linopirdine. These results indicate that linopirdine facilitates and triggers transmitter release via blockade of K M channels and suggest that these K + channels are located at neuronal somata rather than at presynaptic sites.