Inhibitory effects of capsaicin on acetylcholine‐evoked responses in rat phaeochromocytoma cells

The effects of capsaicin on cellular responses evoked by acetylcholine (ACh) and those by adenosine 5′‐triphosphate (ATP) were investigated in rat phaeochromocytoma PC12 cells. Capsaicin (1 to 30 μm) suppressed dopamine release and the intracellular Ca²⁺ increase evoked by 100 μm ACh. The concentration‐dependence of the ACh‐evoked release of dopamine was not shifted but the maximal response was reduced by capsaicin. Dopamine release evoked by 80 mm KC1 was also suppressed by capsaicin (3 and 30 μm), but the extent of suppression was smaller than that of the ACh‐evoked release. Under whole‐cell voltage‐clamp, capsaicin (1 to 30 μm) reversibly inhibited the inward current activated by ACh (30 to 300 μm). The inhibition exhibited dependence on the concentration of ACh, and the current activated by a higher concentration of ACh was less inhibited. Voltage‐dependence of block by capsaicin was not observed when it was tested either by applying a ramp pulse during the current activation by ACh or by eliciting the current in cells held at various potentials. High concentrations of capsaicin (30 to 100 μm) enhanced the inward current as well as dopamine release evoked by 30 μm ATP. The results suggest that low concentrations of capsaicin selectively antagonize responses mediated by nicotinic receptor‐channels without affecting those mediated by purinoceptor‐coupled channels. As the antagonism by capsaicin of the ACh‐evoked responses was observed at concentrations as low as 1 μm, the influence on nicotinic receptors should be taken into account when this compound is used as a pharmacological tool to deplete neuropeptides. 1994 British Pharmacological Society