Article date: March 1991
By: Ping‐Sheng Hu, Bertil B. Fredholm, in Volume 102, Issue 3, pages 764-768
We have examined the mechanisms by which the K+‐channel blocker 4‐aminopyridine (4‐AP) can dose‐dependently increase both basal [3H]‐noradrenaline ([3H]‐NA) release and the [3H]‐NA release evoked by electrical stimulation, but not the release of [3H]‐acetylcholine ([3H]‐ACh), from slices of rat hippocampus.
Both the electrically evoked and the 4‐AP‐induced release were blocked by tetrodotoxin (TTX) (3 μm). The Ca2+‐dependence of the 4‐AP‐induced release (EC50 0.15 mm) was, however, different from that of the electrically evoked [3H]‐NA release (EC50 0.76 mm).
The 4‐AP‐induced release could be inhibited by CdCl2(10 μm) and ω‐conotoxin (30 nm), but not by nifedipine (1 μm).
Transmitter release evoked by 100 μm 4‐AP could be blocked by the α2‐adrenoceptor agonist, UK 14,304 (0.1 μm) and by the A1‐receptor agonist R‐N6‐phenylisopropyl adenosine (R‐PIA, 1 μm) and increased by the α2‐adrenoceptor antagonist, yohimbine (1 μm), both in 0.25 and 1.3 mm Ca2+‐containing medium. By contrast, the effect of α2‐adrenoceptor agonists and antagonists on transmitter release evoked by electrical stimulation was markedly reduced in the presence of 4‐AP (100 μm).
The results suggest that 4‐AP can depolarize some nerve endings in the central nervous system, leading to transmitter release that is dependent on nerve impulses and Ca2+. Furthermore, the fact that α2‐receptors and adenosine A1 receptor agonists can influence the release of NA evoked by 4‐AP suggests that these drugs may have actions that are independent of blockade of aminopyridine‐sensitive K+‐channels.
We have examined the mechanisms by which the K+‐channel blocker 4‐aminopyridine (4‐AP) can dose‐dependently increase both basal [3H]‐noradrenaline ([3H]‐NA) release and the [3H]‐NA release evoked by electrical stimulation, but not the release of [3H]‐acetylcholine ([3H]‐ACh), from slices of rat hippocampus.
Both the electrically evoked and the 4‐AP‐induced release were blocked by tetrodotoxin (TTX) (3 μm). The Ca2+‐dependence of the 4‐AP‐induced release (EC50 0.15 mm) was, however, different from that of the electrically evoked [3H]‐NA release (EC50 0.76 mm).
The 4‐AP‐induced release could be inhibited by CdCl2(10 μm) and ω‐conotoxin (30 nm), but not by nifedipine (1 μm).
Transmitter release evoked by 100 μm 4‐AP could be blocked by the α2‐adrenoceptor agonist, UK 14,304 (0.1 μm) and by the A1‐receptor agonist R‐N6‐phenylisopropyl adenosine (R‐PIA, 1 μm) and increased by the α2‐adrenoceptor antagonist, yohimbine (1 μm), both in 0.25 and 1.3 mm Ca2+‐containing medium. By contrast, the effect of α2‐adrenoceptor agonists and antagonists on transmitter release evoked by electrical stimulation was markedly reduced in the presence of 4‐AP (100 μm).
The results suggest that 4‐AP can depolarize some nerve endings in the central nervous system, leading to transmitter release that is dependent on nerve impulses and Ca2+. Furthermore, the fact that α2‐receptors and adenosine A1 receptor agonists can influence the release of NA evoked by 4‐AP suggests that these drugs may have actions that are independent of blockade of aminopyridine‐sensitive K+‐channels.
DOI: 10.1111/j.1476-5381.1991.tb12247.x
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