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

Jae Hoon Sim, Chul Kim Kim, Sungjoon Kim, Sang Jin Lee, Suk Hyo Suh, Jae Yeoul Jun, Insuk So, Ki Whan Kim

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations. The direct 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 releasing 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 μM). The inhibitory effects of CAP both on the high K+ contracture induced by 50 mM K+ Tyrode solution and on the slow waves recorded using a conventional intracellular microelectrode technique were similar to those of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOCC is decreased by CAP. Ca2+ channel current (IBa) decreased in a concentration-dependent manner on superfusing the physiological salt solution containing various concentrations of CAP. The steady-state activation and inactivation curves of IBa were not affected by the treatment with CAP. The experiment using a synthetic water-soluble analog of CAP, DA-5018·HCl, suggested that the acting site of CAP is present in the intracellular side. Spontaneous 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 associated with the direct inhibitory action on the VOCC from inside of the cell.

Original languageEnglish
Pages (from-to)2347-2360
Number of pages14
JournalLife Sciences
Volume68
Issue number21
DOIs
StatePublished - 13 Apr 2001

Fingerprint

Capsaicin
Calcium Channels
Muscle Cells
Stomach
Guinea Pigs
Electric potential
Muscle
Smooth Muscle
Antral
Microelectrodes
Contracture
Sensory Receptor Cells
Muscle Contraction
Verapamil
Inhibitory Concentration 50
Neurons

Keywords

  • Ca channel current
  • Capsaicin
  • Gastric smooth muscle strip
  • High K contracture
  • Slow waves

Cite this

Sim, Jae Hoon ; Kim, Chul Kim ; Kim, Sungjoon ; Lee, Sang Jin ; Suh, Suk Hyo ; Jun, Jae Yeoul ; So, Insuk ; Kim, Ki Whan. / Capsaicin inhibits the voltage-operated calcium channels intracellularly in the antral circular myocytes of guinea-pig stomach. In: Life Sciences. 2001 ; Vol. 68, No. 21. pp. 2347-2360.
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abstract = "Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations. The direct 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 releasing 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 μM). The inhibitory effects of CAP both on the high K+ contracture induced by 50 mM K+ Tyrode solution and on the slow waves recorded using a conventional intracellular microelectrode technique were similar to those of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOCC is decreased by CAP. Ca2+ channel current (IBa) decreased in a concentration-dependent manner on superfusing the physiological salt solution containing various concentrations of CAP. The steady-state activation and inactivation curves of IBa were not affected by the treatment with CAP. The experiment using a synthetic water-soluble analog of CAP, DA-5018·HCl, suggested that the acting site of CAP is present in the intracellular side. Spontaneous 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 associated with the direct inhibitory action on the VOCC from inside of the cell.",
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Capsaicin inhibits the voltage-operated calcium channels intracellularly in the antral circular myocytes of guinea-pig stomach. / Sim, Jae Hoon; Kim, Chul Kim; Kim, Sungjoon; Lee, Sang Jin; Suh, Suk Hyo; Jun, Jae Yeoul; So, Insuk; Kim, Ki Whan.

In: Life Sciences, Vol. 68, No. 21, 13.04.2001, p. 2347-2360.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Capsaicin inhibits the voltage-operated calcium channels intracellularly in the antral circular myocytes of guinea-pig stomach

AU - Sim, Jae Hoon

AU - Kim, Chul Kim

AU - Kim, Sungjoon

AU - Lee, Sang Jin

AU - Suh, Suk Hyo

AU - Jun, Jae Yeoul

AU - So, Insuk

AU - Kim, Ki Whan

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N2 - Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations. The direct 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 releasing 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 μM). The inhibitory effects of CAP both on the high K+ contracture induced by 50 mM K+ Tyrode solution and on the slow waves recorded using a conventional intracellular microelectrode technique were similar to those of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOCC is decreased by CAP. Ca2+ channel current (IBa) decreased in a concentration-dependent manner on superfusing the physiological salt solution containing various concentrations of CAP. The steady-state activation and inactivation curves of IBa were not affected by the treatment with CAP. The experiment using a synthetic water-soluble analog of CAP, DA-5018·HCl, suggested that the acting site of CAP is present in the intracellular side. Spontaneous 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 associated with the direct inhibitory action on the VOCC from inside of the cell.

AB - Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations. The direct 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 releasing 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 μM). The inhibitory effects of CAP both on the high K+ contracture induced by 50 mM K+ Tyrode solution and on the slow waves recorded using a conventional intracellular microelectrode technique were similar to those of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOCC is decreased by CAP. Ca2+ channel current (IBa) decreased in a concentration-dependent manner on superfusing the physiological salt solution containing various concentrations of CAP. The steady-state activation and inactivation curves of IBa were not affected by the treatment with CAP. The experiment using a synthetic water-soluble analog of CAP, DA-5018·HCl, suggested that the acting site of CAP is present in the intracellular side. Spontaneous 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 associated with the direct inhibitory action on the VOCC from inside of the cell.

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