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Potassium Channel Blockers Inhibit D 2 Dopamine, but Not A 1 Adenosine, Receptor‐Mediated Inhibition of Striatal Dopamine Release
Author(s) -
Cass Wayne A.,
Zahniser Nancy R.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02109.x
Subject(s) - dopamine , autoreceptor , chemistry , tetraethylammonium , adenosine , 4 aminopyridine , agonist , medicine , dopamine receptor , endocrinology , striatum , dopamine receptor d1 , potassium channel , potassium channel blocker , pharmacology , receptor , potassium , biology , biochemistry , organic chemistry
D 2 dopamine autoreceptors and A 1 adenosine heteroreceptors inhibit the evoked release of dopamine from rat striatum. We examined the role of potassium channels in this modulation by determining the effects of two potassium channel blockers, 4‐aminopyridine and tetraethylammonium, on the modulation of electrically stimulated release of endogenous dopamine from rat striatal slices. Maximally effective concentrations of the D 2 dopamine receptor agonist N‐0437 (10 n M ) and of adenosine (50 μ M ) caused a 30% inhibition of evoked dopamine overflow, and their effects were additive. When coperfused with N‐0437, both 4‐aminopyridine and tetraethylammonium blocked the inhibition caused by N‐0437 in a dose‐dependent manner. 4‐Aminopyridine was approximately three orders of magnitude more potent than tetraethylammonium, with complete blockade occurring at 3μ M and 1 m M , respectively. Binding experiments confirmed that neither 4‐aminopyridine nor tetraethylammonium was a direct‐acting D 2 dopamine receptor antagonist at the concentration necessary to block the release‐modulatory effect of D 2 receptor activation. In contrast, the inhibitory modulation produced by adenosine was not affected by 4‐aminopyridine (30 μ M ) or tetraethylammonium (1 m M ). These results suggest that D 2 dopamine and A 1 adenosine receptors inhibit dopamine release in the striatum by different mechanisms. D 2 dopamine autoreceptor action appears to involve potassium channels, whereas A 1 adenosine receptor action does not.