Modulation of acetylcholine release in rat hippocampus by amino alcohols and Bay K 8644.
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.
Bostwick
J R
JR
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Abbe
R
R
Appel
S H
SH
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019856:Ethanolamine; D004983:Ethanolamines / Q000494:pharmacology*; D005444:Flunarizine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014700:Verapamil / Q000494:pharmacology
D004983:Ethanolamines; D011412:Propanolamines; D011759:Pyrrolidines; C010509:prolinol; D019856:Ethanolamine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C034448:2-aminopropanol; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002794:Choline; D000109:Acetylcholine; D005444:Flunarizine; D002118:Calcium