The effect of MR16728, a cetiedil analogue, on acetylcholine release in Torpedo synaptosomes.
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.
Moulian
N
N
Département de Neurochimie, CNRS, Gif-sur-Yvette, France.
Gaudry-Talarmain
Y M
YM
Israël
M
M
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
D000081:Acetamides; D000083:Acetanilides; D001381:Azepines; C080235:MR 16728; D000001:Calcimycin; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D002118:Calcium