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; Yoon, Shin-Hee; Hahn, Sang-June; Rhie, Duck-Joo; Jo, Yang-Hyeok; Kim, Myung-Suk

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자료유형: 학술저널

저자정보: Sim, Sang-Soo (Department of Physiology, Catholic University Medical College) Yoon, Shin-Hee (Department of Physiology, Catholic University Medical College) Hahn, Sang-June (Department of Physiology, Catholic University Medical College) Rhie, Duck-Joo (Department of Physiology, Catholic University Medical College) Jo, Yang-Hyeok (Department of Physiology, Catholic University Medical College) Kim, Myung-Suk (Department of Physiology, Catholic University Medical College)

저널정보: 대한생리학회 대한생리학회지 대한생리학회지 제29권 제1호

발행연도: 1995.1

수록면: 29 - 37 (9page)

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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.

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

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