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The pre-synaptic blocker toosendanin does not inhibit secretion in exocrine cells
1Institute of Cell Biology, Beijing Normal University, Beijing 100875, China. zjcui@bnu.edu.cn
Aim:
Toosendanin is a pre-synaptic blocker at the neuromuscular junction and its inhibitory effect is divided into an initial facilitative/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-2 microfluorometry.
Results:
Effects of toosendanin on CCK-induced amylase secretion and calcium oscillations were investigated. Toosendanin of 87-870 microM had no effect on 10 pM-100 nM CCK-stimulated amylase secretion, nor did 8.7-870 microM toosendanin inhibit 5 pM CCK-induced calcium oscillations. In contrast, 10 nM CCK(1) receptor antagonist FK 480 completely blocked 5 pM 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.