KATP channel blockers selectively interact with A1-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus

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Abstract

In this study the role of ATP-sensitive K+ channels (KATP channels) in the A1 receptor mediated presynaptic inhibitory modulation of acetylcholine release was investigated in the rat hippocampus. N6-Cyclohexyladenosine (CHA), the selective A1-adenosine receptor agonist, reduced concentration-dependently the stimulation-evoked (2 Hz, 1 ms, 240 shocks) [3H]acetylcholine ([3H]ACh) release, from in vitro superfused hippocampal slices preloaded with [3H]choline, an effect prevented by the selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither KATP channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibenclamide and glipizide, the inhibitors of KATP channels, exerted a significant effect on the resting and evoked release of [3H]ACh. Glibenclamide and glipizide (10-100 μM) completely prevented the inhibitory effect of 0.1 μM CHA and shifted the concentration response curve of CHA to the right. 4-Aminopyridine (10-100 μM), the non-selective potassium channel blocker, increased the evoked release of [3H]ACh, but in the presence of 4-aminopyridine, the inhibitory effect of CHA (0.1 μM) still persisted. Oxotremorine, the M2 muscarinic receptor agonist, decreased the stimulation-evoked release of [3H]ACh, but its effect was not reversed by glibenclamide. 1,3-Diethyl-8-phenylxanthine (DPX), the selective A1-antagonist, effectively displaced [3H]DPCPX in binding experiments, while in the case of glibenclamide and glipizide, only slight displacement was observed. In summary, our results suggest that KATP channels are functionally coupled to A1 receptors present on cholinergic terminals of the hippocampus, and glibenclamide and glipizide, by interacting with KATP channels, relieve this inhibitory neuromodulation.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalBrain Research
Volume889
Issue number1-2
DOIs
Publication statusPublished - Jan 19 2001

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Adenosine A1 Receptors
KATP Channels
Glipizide
Glyburide
Acetylcholine
Hippocampus
4-Aminopyridine
Adenosine A1 Receptor Agonists
Pinacidil
Potassium Channel Blockers
Cromakalim
Oxotremorine
Presynaptic Receptors
Diazoxide
Muscarinic Agonists
Choline
Cholinergic Agents
Shock
Adenosine Triphosphate
1,3-dipropyl-8-cyclopentylxanthine

Keywords

  • A-adenosine receptor
  • Acetylcholine release
  • Glibenclamide
  • Hippocampus
  • K channel
  • Neuromodulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "KATP channel blockers selectively interact with A1-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus",
abstract = "In this study the role of ATP-sensitive K+ channels (KATP channels) in the A1 receptor mediated presynaptic inhibitory modulation of acetylcholine release was investigated in the rat hippocampus. N6-Cyclohexyladenosine (CHA), the selective A1-adenosine receptor agonist, reduced concentration-dependently the stimulation-evoked (2 Hz, 1 ms, 240 shocks) [3H]acetylcholine ([3H]ACh) release, from in vitro superfused hippocampal slices preloaded with [3H]choline, an effect prevented by the selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither KATP channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibenclamide and glipizide, the inhibitors of KATP channels, exerted a significant effect on the resting and evoked release of [3H]ACh. Glibenclamide and glipizide (10-100 μM) completely prevented the inhibitory effect of 0.1 μM CHA and shifted the concentration response curve of CHA to the right. 4-Aminopyridine (10-100 μM), the non-selective potassium channel blocker, increased the evoked release of [3H]ACh, but in the presence of 4-aminopyridine, the inhibitory effect of CHA (0.1 μM) still persisted. Oxotremorine, the M2 muscarinic receptor agonist, decreased the stimulation-evoked release of [3H]ACh, but its effect was not reversed by glibenclamide. 1,3-Diethyl-8-phenylxanthine (DPX), the selective A1-antagonist, effectively displaced [3H]DPCPX in binding experiments, while in the case of glibenclamide and glipizide, only slight displacement was observed. In summary, our results suggest that KATP channels are functionally coupled to A1 receptors present on cholinergic terminals of the hippocampus, and glibenclamide and glipizide, by interacting with KATP channels, relieve this inhibitory neuromodulation.",
keywords = "A-adenosine receptor, Acetylcholine release, Glibenclamide, Hippocampus, K channel, Neuromodulation",
author = "B. Sperl{\'a}gh and G. Zsilla and E. V{\'i}zi",
year = "2001",
month = "1",
day = "19",
doi = "10.1016/S0006-8993(00)03110-3",
language = "English",
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pages = "63--70",
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issn = "0006-8993",
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TY - JOUR

T1 - KATP channel blockers selectively interact with A1-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus

AU - Sperlágh, B.

AU - Zsilla, G.

AU - Vízi, E.

PY - 2001/1/19

Y1 - 2001/1/19

N2 - In this study the role of ATP-sensitive K+ channels (KATP channels) in the A1 receptor mediated presynaptic inhibitory modulation of acetylcholine release was investigated in the rat hippocampus. N6-Cyclohexyladenosine (CHA), the selective A1-adenosine receptor agonist, reduced concentration-dependently the stimulation-evoked (2 Hz, 1 ms, 240 shocks) [3H]acetylcholine ([3H]ACh) release, from in vitro superfused hippocampal slices preloaded with [3H]choline, an effect prevented by the selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither KATP channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibenclamide and glipizide, the inhibitors of KATP channels, exerted a significant effect on the resting and evoked release of [3H]ACh. Glibenclamide and glipizide (10-100 μM) completely prevented the inhibitory effect of 0.1 μM CHA and shifted the concentration response curve of CHA to the right. 4-Aminopyridine (10-100 μM), the non-selective potassium channel blocker, increased the evoked release of [3H]ACh, but in the presence of 4-aminopyridine, the inhibitory effect of CHA (0.1 μM) still persisted. Oxotremorine, the M2 muscarinic receptor agonist, decreased the stimulation-evoked release of [3H]ACh, but its effect was not reversed by glibenclamide. 1,3-Diethyl-8-phenylxanthine (DPX), the selective A1-antagonist, effectively displaced [3H]DPCPX in binding experiments, while in the case of glibenclamide and glipizide, only slight displacement was observed. In summary, our results suggest that KATP channels are functionally coupled to A1 receptors present on cholinergic terminals of the hippocampus, and glibenclamide and glipizide, by interacting with KATP channels, relieve this inhibitory neuromodulation.

AB - In this study the role of ATP-sensitive K+ channels (KATP channels) in the A1 receptor mediated presynaptic inhibitory modulation of acetylcholine release was investigated in the rat hippocampus. N6-Cyclohexyladenosine (CHA), the selective A1-adenosine receptor agonist, reduced concentration-dependently the stimulation-evoked (2 Hz, 1 ms, 240 shocks) [3H]acetylcholine ([3H]ACh) release, from in vitro superfused hippocampal slices preloaded with [3H]choline, an effect prevented by the selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither KATP channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibenclamide and glipizide, the inhibitors of KATP channels, exerted a significant effect on the resting and evoked release of [3H]ACh. Glibenclamide and glipizide (10-100 μM) completely prevented the inhibitory effect of 0.1 μM CHA and shifted the concentration response curve of CHA to the right. 4-Aminopyridine (10-100 μM), the non-selective potassium channel blocker, increased the evoked release of [3H]ACh, but in the presence of 4-aminopyridine, the inhibitory effect of CHA (0.1 μM) still persisted. Oxotremorine, the M2 muscarinic receptor agonist, decreased the stimulation-evoked release of [3H]ACh, but its effect was not reversed by glibenclamide. 1,3-Diethyl-8-phenylxanthine (DPX), the selective A1-antagonist, effectively displaced [3H]DPCPX in binding experiments, while in the case of glibenclamide and glipizide, only slight displacement was observed. In summary, our results suggest that KATP channels are functionally coupled to A1 receptors present on cholinergic terminals of the hippocampus, and glibenclamide and glipizide, by interacting with KATP channels, relieve this inhibitory neuromodulation.

KW - A-adenosine receptor

KW - Acetylcholine release

KW - Glibenclamide

KW - Hippocampus

KW - K channel

KW - Neuromodulation

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U2 - 10.1016/S0006-8993(00)03110-3

DO - 10.1016/S0006-8993(00)03110-3

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C2 - 11166687

AN - SCOPUS:0035910325

VL - 889

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JO - Brain Research

JF - Brain Research

SN - 0006-8993

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