Relaxant Effect of Spermidine on Acethylcholine and High $K^+$-induced Gastric Contractions of Guinea-Pig

  • Kim, Young-Chul (Departments of Physiology, Chungbuk National University College of Medicine) ;
  • Sim, Jae-Hoon (Department of Physiology and Biophysics, Seoul National University College of Medicine) ;
  • Choi, Woong (Departments of Pharmacology, Chungbuk National University College of Medicine) ;
  • Kim, Chan-Hyung (Departments of Pharmacology, Chungbuk National University College of Medicine) ;
  • You, Ra-Young (Departments of Physiology, Chungbuk National University College of Medicine) ;
  • Xu, Wen-Xie (Department of Physiology, College of Medicine, Shanghai Jiaotong University) ;
  • Lee, Sang-Jin (Departments of Physiology, Chungbuk National University College of Medicine)
  • Published : 2008.04.30

Abstract

In our previous study, we found that spermine and putrescine inhibited spontaneous and acetylcholine (ACh)-induced contractions of guinea-pig stomach via inhibition of L-type voltage- dependent calcium current ($VDCC_L$). In this study, we also studied the effect of spermidine on mechanical contractions and calcium channel current ($I_{Ba}$), and then compared its effects to those by spermine and putrescine. Spermidine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner ($IC_{50}=1.1{\pm}0.11mM$). Relationship between inhibition of contraction and calcium current by spermidine was studied using 50 mM high $K^+$-induced contraction: Spermidine (5 mM) significantly reduced high $K^+$ (50 mM)-induced contraction to 37${\pm}$4.7% of the control (p<0.05), and inhibitory effect of spermidine on $I_{Ba}$ was also observed at a wide range of test potential in current/voltage (I/V) relationship. Pre- and post-application of spermidine (5 mM) also significantly inhibited carbachol (CCh) and ACh-induced initial and phasic contractions. Finally, caffeine (10 mM)-induced contraction which is activated by $Ca^{2+}$-induced $Ca^{2+}$ release (CICR), was also inhibited by pretreatment of spermidine (5 mM). These findings suggest that spermidine inhibits spontaneous and CCh-induced contraction via inhibition of $VDCC_L$ and $Ca^{2+}$ releasing mechanism in guinea-pig stomach.

Keywords

References

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