AIM：Toosendanin is a pre-synaptic blocer at the neuromuscular junction and its inhititory effect is divided into an initial facilitatve/stimulatory phase followed by a prolonged inhibitory phase,The present study inv...AIM：Toosendanin is a pre-synaptic blocer at the neuromuscular junction and its inhititory effect is divided into an initial facilitatve/stimulatory phase followed by a prolonged inhibitory phase,The present study investigated whether the subsequent inhibitory phase was due to exhaustion of the secretory machinery as a result of extensive stimulation during the initial facilitative phase More specifically,this paper examined whether toosendanin could directly inhibit the secretory machinery in exocrine cells.METHODS:Rat pancreatic acinar cells were isolated by collagenase digestion,Secretion was assessed by measuring the amount of amylase released into the extracellular medium as a percentage of the total present in the cells before stimulation.Cholecystokinin(CCK)-induced increases in intracellular calcium in single cells were measured with fura-2microfluorometry.RESULTS:Effects of toosendanin on CCK-induced amylase secretion and calcium oscillations were investigated.Toosendanin of 87-870μMhad no effect on 10pM-100nMCCK-stimulated amylase secretion.nor did 8.7-870μMtoosendanin inhibit 5pM CCK-induced calcium oscillations.In contrast,10nMCCK1recepto antagonistFK480completely blocked5pM CCK-induced calcium oscillations.CONCLUSION;The pre-synaptic“blocker”toosendanin is a selective activator of the voltage-dependent calcium channels but does not interfere with the secretory machinery itself.展开更多
基金Natural Science Foundation of China Grant No.39870367,39825112,30070286The Ph.D.Program of the Ministry of Education,China.
文摘AIM：Toosendanin is a pre-synaptic blocer at the neuromuscular junction and its inhititory effect is divided into an initial facilitatve/stimulatory phase followed by a prolonged inhibitory phase,The present study investigated whether the subsequent inhibitory phase was due to exhaustion of the secretory machinery as a result of extensive stimulation during the initial facilitative phase More specifically,this paper examined whether toosendanin could directly inhibit the secretory machinery in exocrine cells.METHODS:Rat pancreatic acinar cells were isolated by collagenase digestion,Secretion was assessed by measuring the amount of amylase released into the extracellular medium as a percentage of the total present in the cells before stimulation.Cholecystokinin(CCK)-induced increases in intracellular calcium in single cells were measured with fura-2microfluorometry.RESULTS:Effects of toosendanin on CCK-induced amylase secretion and calcium oscillations were investigated.Toosendanin of 87-870μMhad no effect on 10pM-100nMCCK-stimulated amylase secretion.nor did 8.7-870μMtoosendanin inhibit 5pM CCK-induced calcium oscillations.In contrast,10nMCCK1recepto antagonistFK480completely blocked5pM CCK-induced calcium oscillations.CONCLUSION;The pre-synaptic“blocker”toosendanin is a selective activator of the voltage-dependent calcium channels but does not interfere with the secretory machinery itself.
