Stimulatory effect of trans-cinnamaldehyde on norepinephrine secretion in cultured pheochromocytoma (PC-12) cells.
AIM
The effect of trans-cinnamaldehyde (CNMA) on the release of norepinephrine (NE) from nerve terminal was investigated using rat pheochromocytoma 12 (PC-12) cells.


METHODS
The amount of NA released from PC-12 cells incubated with CNMA or related substances was quantified by high performance liquid chromatography (HPLC)-electrochemical detection. The lipophilic anion bisoxonol was used to monitor the effect of CNMA on the membrane potential.


RESULTS
CNMA stimulated the secretion of NE in a concentration-dependent manner from 5 mumol/L to 50 mumol/L, while the value of lactate dehydrogenase in the incubated medium was not influenced by CNMA. However, acetaldehyde, cinnamic acid, cinnamoyl chloride and cinnamamide failed to produce similar effect. The action of CNMA can thus be considered specific. The depolarizing effect of CNMA on the membrane potential was also illustrated by a concentration-dependent increase in the fluorescence of bisoxonol, a potential-sensitive dye. Saxitoxin attenuated the depolarizing action of CNMA at concentrations sufficient to block sodium channels. Besides, the effect of CNMA to depolarize the membrane potential in PC-12 cells is greater than that of 4-aminopyridine (4-AP). The action of CNMA on NE releasing depends on extracellular Ca2+ and is attenuated by 8-bromo-cAMP at concentrations sufficient to inhibit the action of cyclic AMP.


CONCLUSION
These findings suggest that CNMA can depolarize the membrane to result in a Ca(2+)-dependent and cyclic AMP-related release of NE from PC-12 cells.