Capsaicin inhibits the voltage-operated calcium channels intracellularly in the antral circular myocytes of guinea-pig stomach

Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations, The dir ect effect of CAP on gastric smooth muscle itself has not yet been reported , though CAP was reported to relax the isolated guinea-pig stomach by relea sing nitric oxide from the CAP-sensitive sensory neurons. Here we showed an evidence that CAP evokes a prolonged relaxation of gastric antral circular smooth muscle(CAP-induced relaxation) by blocking the voltage-operated Ca2 + channels (VOCC) from inside of the cell. CAP suppressed dose-dependently the spontaneous contractions of guinea-pig gastric circular muscle strip under the condition without neural influence (IC50 = 5.8 muM) The inhibitory effects of CAP both on the high K+ contract ure induced by 50 mM K+ Tyrode solution and on the slow waves recorded usin g a conventional intracellular microelectrode technique were similar to tho se of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOC C is decreased by CAP. Ca2+ channel current (I-Ba) decreased in a concentra tion-dependent manner on superfusing the physiological salt solution contai ning various concentrations of CAP. The steady-state activation and inactiv ation curves of I-Ba were not affected by the treatment with CAP. The exper iment using a synthetic water-soluble analog of CAP, DA-5018 . HCl, suggest ed that the acting site of CAP is present in the intracellular side. Sponta neous transient outward K+ currents(STOCs) recorded at a holding potential of 0 mV were also inhibited by CAP and verapamil, Ca channel blocker. Taken together, these results indicate that CAP-induced relaxation is assoc iated with the direct inhibitory action on the VOCC from inside of the cell . (C) 2001 Elsevier Science Inc. All rights reserved.