title: The effect of MR16728, a cetiedil analogue, on acetylcholine release in Torpedo synaptosomes.
abstract: MR16728, a cetiedil analogue, enhanced acetylcholine (ACh) release (up to 145% of control) from Torpedo synaptosomes when the release was triggered by a Ca2+ ionophore, A23187 or ionomycin, in the presence of 4 mM Ca2+ in the release medium, but inhibited ACh release induced by KCl depolarization of the presynaptic membrane. MR16728 also inhibited Ca(2+)-ATPase activity measured in purified synaptosomal presynaptic membranes. We studied the stimulation by MR16728 as a function of its concentration; the half-maximal effect was reached at the concentration of 13.5 microM. Moreover the stimulation was more pronounced (up to 300%) when a low concentration of Ca2+ (in the 10-micromolar range) was added to the medium. The enhancement of ACh release was also observed in proteoliposomes having incorporated mediatophore, a presynaptic membrane protein, able to release ACh in a Ca(2+)-dependent manner. Thus, mediatophore is a potential presynaptic target for MR16728.
authors.affiliation: Département de Neurochimie, CNRS, Gif-sur-Yvette, France.
authors.forename: N
authors.initials: N
authors.lastname: Moulian
authors.forename: Y M
authors.initials: YM
authors.lastname: Gaudry-Talarmain
authors.forename: M
authors.initials: M
authors.lastname: Israël
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000083:Acetanilides; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo
chemical_list: D000081:Acetamides; D000083:Acetanilides; D001381:Azepines; C080235:MR 16728; D000001:Calcimycin; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium