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

Abstract

The inhibitory effect of an adenosine analogue, R-PIA, and an .alpha.2-adrenoceptor agonist, UK 14,304, on [3H]NA efflux from field-stimulated rat hippocampal slices was examined. The effect of 0.1 .mu.M UK 14,304 was mimicked by 30 nM .omega.-conotoxin and by 10 .mu.M cadmium chloride, inhibitors of N- and L-type Ca2+ channels. R-PIA (1 .mu.M) had no effect per se, but caused a clear-cut inhibition after blockade of the pre-synaptic .alpha.2-receptor by yohimbine. 4-Aminopyridine (4-AP) caused a dose-dependent increase in evoked transmitter release. At 30 .mu.M 4-AP did not affect the actions of .omega.-conotoxin or cadmium chloride. The pre-synaptic effect of UK 14,304 was virtually abolished by 4-AP (30 .mu.M). The effect of UK 14,304 (1.0 .mu.M) 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 .mu.M) was decreased by 4-AP in a concentration-dependent manner from 142% increase in controls to 21% at 100 .mu.M 4-AP. The present results indicate that NA release is reduced by somewhat different mechanisms by pre-synaptic .alpha.2- and adenosine A1-receptors. Furthermore, the results indicate that pre-synaptic A1-receptors on hippocampal NA neurons do not primarily regulate 4-AP-dependent potassium channels, but they might act directly on a Ca2+ conductance.