flunarizine and prolinol

The amino alcohols ethanolamine, R-alaninol and R-prolinol were shown to enhance high potassium evoked release of [3H]acetylcholine from hippocampal slices by monitoring fractional release of tritium during superfusion. This action appeared to be unique to hippocampal cholinergic nerve terminals because R-prolinol did not modulate evoked release of acetylcholine from cortical or striatal slices, dopamine from striatal slices or norepinephrine from hippocampal slices. Bay K 8644, a dihydropyridine activator of calcium L-channels, exhibited a similar specificity profile. Bay K 8644 decreased the EC50 of R-prolinol without changing the maximal response, indicating that the actions of these two compounds converge through a common cellular mechanism. The effect of R-prolinol was blocked by the L-channel antagonists diltiazem and verapamil but not by nifedipine. In contrast, nifedipine only and not diltiazem or verapamil, blocked the enhancement induced by Bay K 8644. It appears then that amino alcohols can modulate the release of acetylcholine in the hippocampus possibly by enhancing calcium entry into nerve terminals through a specific activation of presynaptic L-channels at a site other than that which interacts with dihydropyridines.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Acetylcholine; Animals; Calcium; Cerebral Cortex; Choline; Corpus Striatum; Diltiazem; Dose-Response Relationship, Drug; Ethanolamine; Ethanolamines; Flunarizine; Hippocampus; In Vitro Techniques; Male; Nifedipine; Osmolar Concentration; Potassium Chloride; Propanolamines; Pyrrolidines; Rats; Rats, Inbred F344; Verapamil