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Inhibitory Effects of Verapamil and TMB-8 on Tonic Contraction Are Accompanied by Inhibition of Phospholipase C Activity in Intact Gastric Smooth Muscle Cells

Sim, Sang-Soo   (Department of Physiology, Catholic University Medical CollegeUU0013933  ); Yoon, Shin-Hee   (Department of Physiology, Catholic University Medical CollegeUU0013933  ); Hahn, Sang-June   (Department of Physiology, Catholic University Medical CollegeUU0013933  ); Rhie, Duck-Joo   (Department of Physiology, Catholic University Medical CollegeUU0013933  ); Jo, Yang-Hyeok   (Department of Physiology, Catholic University Medical CollegeUU0013933  ); Kim, Myung-Suk   (Department of Physiology, Catholic University Medical CollegeUU0013933  );
  • 초록

    Gastric smooth muscle of guinea pigs was used to investigate whether the inhibitory effect of calcium antagonists on tonic contraction was accompanied by inhibition of phospholipase C activity. Tonic contraction and $[^{3}H]$ inositol phosphate (IP) formation in response to acetylcholine were measured after pretreatment with verapamil, nifedipine, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxy-benzoate (TMB-8) or EGTA. Verapamil $(10\;{\mu}M)$ , TMB-8 $(10\;{\mu}M)$ or EGTA (2 mM) significantly inhibited acetylcholine $(1\;{\mu}M)$ -stimulated tonic contraction but nifedipine (100 nM) did not. Acetylcholine dose-dependently increased the formation of $[^{3}H]IP$ . This effect was not observed in the presence of 2 mM EGTA. Both verapamil and TMB-8 significantly inhibited $[^{3}H]IP$ formation induced by $10\;{\mu}M$ acetylcholine, whereas nifedipine did not. In a subsequent study, we measured phospholipase C activity in gastric muscle cell homogenate and in permeabilized cells to determine whether calcium antagonists could inhibit the activity directly. The calcium antagonists did not change the phospholipase C activity of the cell homogenate or the permeabilized cells. But EGTA decreased phospholipase C activity by 50%. These results suggest that the inhibitory effects of verapamil and TMB-8 on acetylcholine-stimulated tonic contraction may be accompanied by inhibition of phospholipase C activity.


  • 주제어

    Verapamil .   Nifedipine .   TMB-8 .   Phospholipase C .   Gastric muscle contraction.  

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  • Hahn, Sang-June (11)

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