1. Recently, we suggested that the D2-dopamine receptor involved in the inhibition of evoked [3H]-acetylcholine release from rat striatum is coupled to K+-channels. 2. In the present study, an attempt was made to elucidate further the role of these K+-channels, using the K+-channel blocking agents tetraethylammonium and 4-aminopyridine. With a superfusion method, the effects of both drugs on the D2-dopamine receptor-mediated inhibition of the electrically evoked release of [3H]-acetylcholine from rat striatal tissue slices was investigated. 3. Both tetraethylammonium (30 mM) and 4-aminopyridine (0.1 mM) significantly stimulated the electrically evoked release of [3H]-acetylcholine and completely abolished the effect of the selective D2-receptor agonist LY 171555 (1 microM) on evoked acetylcholine release. In addition, tetraethylammonium (0.03-30 mM) and 4-aminopyridine (0.003-1 mM) strongly increased the basal (non-evoked) release of radioactivity in a concentration-dependent manner. The results suggest that the effect of the drugs on the basal release of radioactivity and on the electrically evoked release of acetylcholine cannot exclusively be explained by their action on K+-channels. 4. Furthermore, with the use of a receptor binding assay, data were obtained on the affinity of tetraethylammonium and 4-aminopyridine for D2-receptors and various other neurotransmitter recognition sites. At concentrations in which both drugs are known to block K+-channels, they were found to inhibit the specific binding of selective radioligands to their respective recognition sites. 5. It is concluded that due to their 'side-effects', both tetraethylammonium and 4-aminopyridine are of only limited value in the investigation of the alleged interaction between neurotransmitter receptors and K+-channels.
|Number of pages||6|
|Journal||British Journal of Pharmacology|
|Publication status||Published - Sep 1989|