The pre-synaptic blocker toosendanin does not inhibit secretion in exocrine cells.
OBJECTIVE
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.


CONCLUSIONS
The pre-synaptic "blocker" toosendanin is a selective activator of the voltage-dependent calcium channels, but does not interfere with the secretory machinery itself.
Cui
Zong-Jie
ZJ
Institute of Cell Biology, Beijing Normal University, Beijing 100875, China. zjcui@bnu.edu.cn
He
Xue-Hui
XH
D000681:Amylases / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D014315:Triterpenes
D000681:Amylases; D015220:Calcium Channels; D002766:Cholecystokinin; D004365:Drugs, Chinese Herbal; C036454:toosendanin; D014315:Triterpenes