α2‐Aclrenoceptor agonist‐mediated inhibition of [3H]noradrenaline release from rat hippocampus is reduced by 4‐aminopyridine, but that caused by an adenosine analogue or co‐conotoxin is not

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Abstract
The inhibitory effect of an adenosine analogue, R‐PIA, and an α2‐adrenoceptor agonist, UK 14,304, on [3H]NA efflux from field‐stimulated rat hippocampal slices was examined. The effect of 0.1 μm UK 14,304 was mimicked by 30 nM w‐conotoxin and by 10 μM cadmium chloride, inhibitors of N‐ and L‐type Ca2+ channels. R‐PIA (1 μM) had no effect per se, but caused a clear‐cut inhibition after blockade of the pre‐synaptic α2‐receptor by yohimbine.4‐Aminopyridine (4‐AP) caused a dose‐dependent increase in evoked transmitter release. At 30 μM 4‐AP did not affect the actions of ω‐conotoxin or cadmium chloride. The pre‐synaptic effect of R‐PIA was similarly unaffected by 30 μM 4‐AP. The presynaptic effect of UK 14,304 was virtually abolished by 4‐AP (30 μM). The effect of UK 14,304 (0.1 μM) could be partly restored by reducing the Ca2+ concentration during treatment with 4‐AP (22% inhibition compared to 42% with normal Ca2+). The magnitude of increase in evoked [3H]NA efflux by yohimbine (1 μM) was decreased by 4‐AP in a concentration‐dependent manner from 142% increase in controls to 21 % at 100 μM 4‐AP.The present results indicate that NA release is reduced by somewhat different mechanisms by pre‐synaptic α2‐ and adenosine Aj‐receptors. Furthermore, the results indicate that pre‐synaptic Arreceptors on hippocampal NA neurons do not primarily regulate 4‐AP‐dependent potassium channels, but they might act directly on a Ca2+ conductance.