PT  - JOURNAL ARTICLE
AU  - Choi, Se-Young
AU  - Kim, Kyong-Tai
TI  - Capsaicin Inhibits Phospholipase C-Mediated Ca<sup>2+</sup>Increase by Blocking Thapsigargin-Sensitive Store-Operated Ca<sup>2+</sup>  Entry in PC12 Cells
DP  - 1999 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 107--114
VI  - 291
IP  - 1
4099  - http://jpet.aspetjournals.org/content/291/1/107.short
4100  - http://jpet.aspetjournals.org/content/291/1/107.full
SO  - J Pharmacol Exp Ther1999 Oct 01; 291
AB  - Capsaicin has been shown to act through vanilloid receptors, which are temperature-sensitive cation channels. However, there also are indications that suggest the capsaicin effect is not mediated by the vanilloid receptor. We therefore investigated the effect of capsaicin on the phospholipase C-mediated Ca2+ rise in PC12 cells. Capsaicin caused a rapid decline in extracellular ATP- or bradykinin-induced calcium transients to the basal level without significant attenuation of the peak level. However, capsaicin did not inhibit either ATP- or bradykinin-induced Ca2+ elevation in the absence of extracellular Ca2+ or inositol-1,4,5-trisphosphate production. Capsaicin also inhibited ATP-induced norepinephrine secretion. Capsaicin dramatically reduced the thapsigargin-induced sustained Ca2+ level, suggesting that capsaicin inhibits thapsigargin-sensitive store-operated Ca2+ entry (SOCE). Thapsigargin-induced Ba2+and Mn2+ influx was also inhibited by capsaicin. Furthermore, capsaicin overlapped SK&F96365 in inhibiting thapsigargin-sensitive SOCE. Capsaicin-induced inhibition of SOCE also occurred in thapsigargin-treated Jurkat-T cells, which have a rather prominent SOCE. Resiniferatoxin, a vanilloid receptor agonist, did not mimic the effect of capsaicin. Ruthenium red and capsazepine, which are known to inhibit the vanilloid receptor, did not affect this capsaicin effect. The results suggest that capsaicin does not mediate vanilloid receptor signaling when inhibiting the thapsigargin-sensitive SOCE. The capsaicin action was also not mediated by activation of protein kinase C because phorbol-12-myristate 13-acetate and capsaicin did not overlap each other’s effect and GF109203X did not reverse the inhibitory effect of capsaicin. The results suggest that capsaicin negatively modulates thapsigargin-sensitive SOCE subsequent to phospholipase C activation. The American Society for Pharmacology and Experimental Therapeutics