Cetiedil, a drug that inhibits acetylcholine release in Torpedo electric organ.
The effects of cetiedil, a vasodilatator substance with reported anticholinergic properties, were examined on cholinergic presynaptic functions at the nerve electroplaque junction of Torpedo marmorata using either synaptosomes or slices of intact tissue. Cetiedil abolished the calcium-dependent release of acetylcholine (ACh) triggered by depolarization or by addition of A23187 ionophore, a finding localizing the site of action downstream from the calcium entry step. In addition, a direct effect on the release process itself was indicated by the observation that cetiedil blocks the release of ACh mediated by a recently isolated presynaptic membrane protein, the mediatophore, reconstituted into ACh-containing proteoliposomes. In all three preparations, ACh release was inhibited by cetiedil with a Ki of 5-8 microM. Under the conditions used in these release experiments, the synthesis of ACh and its compartmentation within the nerve terminals were not modified. However, the drug was able to reduce high-affinity choline uptake and vesicular ACh incorporation when it was given together with the radioactive precursor, a result showing that cetiedil has a broad inhibitory action on cholinergic uptake processes.
D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D011510:Proteolipids; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014101:Torpedo; D014665:Vasodilator Agents / Q000494:pharmacology*
D001381:Azepines; D008081:Liposomes; D011510:Proteolipids; D014665:Vasodilator Agents; C020485:proteoliposomes; C006955:cetiedil; D002794:Choline; D000109:Acetylcholine