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
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.