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Linopirdine (DuP 996) selectively enhances acetylcholine release induced by high potassium, but not electrical stimulation, in rat brain slices and guinea pig ileum
Author(s) -
Smith Craig P.,
Brougham Linda R.,
Vargas Hugo M.
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430290403
Subject(s) - acetylcholine , stimulation , ileum , chemistry , cholinergic , depolarization , choline , medicine , endocrinology , potassium , neurotransmission , pharmacology , biology , biochemistry , organic chemistry , receptor
Abstract The enhancement of acetylcholine (ACh) release during electrical or potassium depolarization was compared in the presence of either linopirdine or 4‐aminopyridine (4‐AP) using two different functional assays. We measured ACh and choline (Ch) directly from striatal perfusates using high performance liquid chromatography and electrochemical detection or indirectly by measuring ACh‐mediated twitch height changes in the electrically stimulated guinea pig ileum. Potassium‐induced twitch responses were also measured in resting ileal segments. Linopirdine significantly enhanced ACh release in the presence of elevated potassium levels in rat striatal slices and guinea pig ileum, but had no effect during electrical stimulation in either model. In contrast, 4‐AP enhanced ACh release in both electrically stimulated striatal slices and ileal strips. In agreement with other studies, atropine enhanced ACh release during either electrical or potassium stimulation paradigms in the striatal slice. The in vitro observations in this report suggest that linopirdine has limited ability to augment the cholinergic neurotransmission evoked by electrical stimulation. © 1993 Wiley‐Liss, Inc.