K-ATP channel blockers selectively interact with A(1)-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus

Citation
B. Sperlagh et al., K-ATP channel blockers selectively interact with A(1)-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus, BRAIN RES, 889(1-2), 2001, pp. 63-70
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
889
Issue
1-2
Year of publication
2001
Pages
63 - 70
Database
ISI
SICI code
0006-8993(20010119)889:1-2<63:KCBSIW>2.0.ZU;2-Z
Abstract
In this study the role of ATP-sensitive K+ channels (K-ATP channels) in the A(1) receptor mediated presynaptic inhibitory modulation of acetylcholine release was investigated in the rat hippocampus. N-6-Cyclohexyladenosine (C HA), the selective A(1)-adenosine receptor agonist, reduced concentration-d ependently the stimulation-evoked (2 Hz, 1 ms, 240 shocks) [H-3]acetylcholi ne ([H-3]ACh) release, from in vitro superfused hippocampal slices preloade d with [H-3]choline an effect prevented by the selective A, receptor antago nist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither K- ATP channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibencl amide and glipizide, the inhibitors of K-ATP channels, exerted a significan t effect on the resting and evoked release of [H-3]ACh. Glibenclamide and g lipizide (10-100 muM) completely prevented the inhibitory effect of 0.1 muM CHA and shifted the concentration response curve of CHA to the right. 4-Am inopyridine (10-100 muM), the non-selective potassium channel blocker, incr eased the evoked release of [H-3]ACh, but in the presence of 4-aminopyridin e, the inhibitory effect of CHA (0.1 muM) still persisted. Oxotremorine, th e M-2 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 A, antagonist, effectively displaced [H-3]DPCPX in binding experiments, while in the case of glibenclamide and g lipizide, only slight displacement was observed. In summary, our results su ggest that K-ATP channels are functionally coupled to A(1) receptors presen t on cholinergic terminals of the hippocampus, and glibenclamide and glipiz ide, by interacting with K-ATP channels, relieve this inhibitory neurumodul ation. (C) 2001 Elsevier Science B.V. All rights reserved.