DIFFERENTIAL SENSITIVITY TO BLOCKADE BY 4-AMINOPYRIDINE OF PRESYNAPTIC RECEPTORS REGULATING [H-3] ACETYLCHOLINE-RELEASE FROM RAT HIPPOCAMPUS

The inhibitory effect of an adenosine analogue, R‐N6‐phenylisopropyl adenosine (R‐PIA), of the cholinergic agonist carbachol, and of morphine on 3H efflux from [3H]choline‐labeled field‐stimulated rat hippocampal slices was compared with that produced by two inhibitors of N‐and L‐type Ca2+ channels, ω‐conotoxin (CgTx; conotoxin GVIA) and cadmium chloride. 4‐Aminopyridine (4‐AP) caused a dose‐dependent increase in evoked transmitter release, with a maximal effect (an almost threefold increase) at 100 μM. 4‐AP (100 μM) did not affect the actions of CgTx, cadmium chloride, and R‐PIA but almost abolished the effect of carbachol and morphine. The present results indicate that presynaptic muscarinic and opiate receptors reduce acetylcholine release by a mechanism that is somewhat different from that used by adenosine A1 receptors. Furthermore, the results indicate that presynaptic A1 receptors on hippocampal cholinergic neurons do not primarily regulate 4‐AP‐dependent potassium channels, but that they might act directly on a Ca2+ conductance. Copyright © 1990, Wiley Blackwell. All rights reserved