SIMILARITIES AND DIFFERENCES IN THE CURRENTS ACTIVATED BY CAPSAICIN, PIPERINE, AND ZINGERONE IN RAT TRIGEMINAL GANGLION-CELLS

1. Capsaicin, piperine, and zingerone are natural pungent-tasting comp ounds found in chili pepper, black pepper, and ginger, respectively. T hese structurally related compounds evoke many of the same physiologic al responses, but at comparable concentrations capsaicin produces comp lete tachyphylaxis, piperine produces partial tachyphylaxis, and zinge rone can either induce or not induce tachyphylaxis. Whole cell patch-c lamp studies were performed on rat trigeminal ganglion cells to determ ine the similarities and differences between these three pungent compo unds. 2. Capsaicin (1 mu M) activated a variety of inward currents hav ing peak times ranging from 2 to 46 s that desensitized to various ext ents ranging from 0 to 100%. The inward currents activated by zingeron e (30 mM) had peak times of similar to 2 s and all currents exhibited marked desensitization. The inward currents activated by piperine (100 mu M) had peak times of similar to 25 s and all exhibited a small des ensitization. 3. Piperine- and zingerone-induced currents were found o nly in cells that could be activated by capsaicin. 4. Capsazepine (10 mu M), an established antagonist of capsaicin-induced currents, inhibi ted the currents evoked by piperine and zingerone, suggesting that all three compounds activate vanilloid receptors. 5. Dose-response relati onships for capsaicin, piperine, and zingerone obtained at a holding p otential of -60 mV had threshold and apparent dissociation constants o f 0.1 and 0.68 mu M, 3 and 35 mu M, and 1 and 15 mM, respectively. The se values were consistent with those previously obtained in behavioral studies.6. After seven 30-s applications of 1 mu M capsaicin or 100 m u M piperine (in a buffer with 2 mM Ca2+), each interspersed with 2 mi n, 50-s washes, the peak currents were inhibited by -60 and 40%, respe ctively. In contrast, 30 mM zingerone failed to evoke a current after six applications. After complete tachyphylaxis produced by 30 mM zinge rone, 1 mu M capsaicin failed to evoke a current, suggesting that thes e two compounds cross desensitize. 7. The similar physiological respon ses produced by these three compounds can be rationalized by their bin ding to receptors and activating currents that can all be inhibited by capsazepine. Their different physiological responses evoked by these compounds can be rationalized. in part, by their very different activa tion and desensitization kinetics, and perhaps by the existence of dif ferent subtypes of vanilloid receptors.