Polygodial is a natural
sesquiterpene which exhibits pronounced pungency and a powerful antifeedant activity. At low concentrations, which do not alter general cell membrane permeability,
polygodial increases the intracellular concentration of free
calcium ([Ca(2+)](i)). Sensory neurotransmission depends on
noradrenaline (NA) release, and vesicular exocytosis, in turn, is dependent on an increase in [Ca(2+)](i). The nociceptive response induced by
polygodial could therefore be directly linked to intracellular
calcium levels. Consequently, the objective of this work was to investigate the effect of
polygodial on NA release. The human
neuroblastoma cell line SH-SY5Y was selected as an in vitro model for sensory neurones. Semiconfluent cells were preloaded with tritiated NA ([(3)H]NA). After 3 min exposure of
polygodial to the cells, released and unreleased radioactivity were measured.
Polygodial induced a significant [(3)H]NA release at concentrations between 0.1 and 0.5 mug/ml with a maximum effect at 0.2 mug/ml (40% increased release of [(3)H]NA as compared with unstimulated control cells). No
polygodial-induced transmitter release was seen at 3.5 and 5 mug/ml. For comparison,
carbachol (1 rim) increased [(3)H]NA release by 10% and the KCl-induced (100 mm) [(3)H]NA release increased by 8% as compared with unstimulated SH-SY5Y cells. In conclusion
polygodial, at the concentrations 0.1-0.5 mug/ml (equal to 0.4-2 mum), induces NA release which is dependent on
polygodial-induced increase in [Ca(2+)](i).