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Investigations into neuropeptide Y‐mediated presynaptic inhibition in cultured hippocampal neurones of the rat
Author(s) -
Bleakman David,
Harrison Neil L.,
Colmers William F.,
Miller Richard J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb12747.x
Subject(s) - cnqx , hippocampal formation , chemistry , neurotransmission , endocrinology , excitatory postsynaptic potential , medicine , tetrodotoxin , glutamatergic , neuropeptide y receptor , neuroscience , agonist , biophysics , biology , neuropeptide , ampa receptor , receptor , glutamate receptor , inhibitory postsynaptic potential , biochemistry
1 We have examined the effects of neuropeptide Y (NPY) on synaptic transmission and [Ca 2+ ] i signals in rat hippocampal neurones grown in culture. [Ca 2+ ] i in individual neurones displayed frequent spontaneous fluctuations often resulting in an elevated plateau [Ca 2+ ] i . These fluctuations were reduced by tetrodotoxin (1 μ m ) or combinations of the excitatory amino acid antagonists 6‐cyano‐7‐dinitroquinoxaline (CNQX) (10 μ m ) and aminophosphonovalerate (APV) (50 μ m ), indicating that they were the result of glutamatergic transmission occurring between hippocampal neurones. 2 [Ca 2+ ] i fluctuations were also prevented by Ni 2+ (200 μ m ), by the GABA B receptor agonist, baclofen (10 μ m ) and by NPY (100 n m ) or Y 2 receptor‐selective NPY agonists. Following treatment of cells with pertussis toxin, NPY produced only a brief decrease in [Ca 2+ ] i fluctuations which rapidly recovered. 3 Perfusion of hippocampal neurones with 50 m m K + produced a large rapid increase in [Ca 2+ ] i . This increase was slightly reduced by NPY or by a combination of CNQX and APV. The effects of CNQX/APV occluded those of NPY. NPY had no effect on Ba 2+ currents measured in hippocampal neurones under whole cell voltage‐clamp even in the presence of intracellular GTP‐γ‐S. On the other hand, Ba 2+ currents were reduced by both Cd 2+ (200 μ m ) and baclofen (10 μ m ). 4 Current clamp recordings from hippocampal neurones demonstrated the occurrence of spontaneous e.p.s.ps and action potential firing which were accompanied by increases in [Ca 2+ ] 4 . This spontaneous activity and the accompanying [Ca 2+ ] i signals were prevented by application of NPY (100 n m ). When hippocampal neurones were induced to fire trains of action potentials in the absence of synaptic transmission, these were accompanied by an increase in cell soma [Ca 2+ ] i . NPY (100 n m ) had no effect on these cell soma [Ca 2+ ] i signals. NPY (100 n m ) also had no effect on inward currents generated in hippocampal neurones by micropipette application of glutamate (50 μ m ). 5 Thus, NPY is able to abolish excitatory neurotransmission in hippocampal cultures through a pertussis toxin‐sensitive mechanism. However, no effect of NPY on Ca 2+ influx into the cell soma of these hippocampal neurones could be discerned. These results are consistent with a localized presynaptic inhibitory effect of NPY on glutamate release in hippocampal neurones in culture.