| 11166687 |
Sperlagh B, Zsilla G, Vizi ES: K (ATP) channel blockers selectively interact with A (1)-adenosine receptor mediated modulation of acetylcholine release in the rat hippocampus. Brain Res. 2001 Jan 19;889(1-2):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 (CHA), the selective A (1)-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 A (1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). By themselves, neither K (ATP) channel openers, i.e. diazoxide, pinacidil and cromakalim, nor glibenclamide and glipizide, the inhibitors of K (ATP) channels, exerted a significant effect on the resting and evoked release of [3H] ACh. Glibenclamide and glipizide (10-100 microM) completely prevented the inhibitory effect of 0.1 microM CHA and shifted the concentration response curve of CHA to the right. 4-Aminopyridine (10-100 microM), 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 microM) still persisted. Oxotremorine, the 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 (1)-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 K (ATP) channels are functionally coupled to A (1) receptors present on cholinergic terminals of the hippocampus, and glibenclamide and glipizide, by interacting with K (ATP) channels, relieve this inhibitory neuromodulation. |
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