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KMID : 0358619950290010029
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Korean Journal of Physiology
1995 Volume.29 No. 1 p.29 ~ p.37
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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
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Sim Sang-Soo
Yoon Shin-Hee
Hahn Sang-June
Rhie Duck-Joo
Jo Yang-Hyeok
Kim Myung-Suk
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Abstract
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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 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 , TMB-8 or EGTA (2 mM) significantly inhibited acetylcholine -stimulated tonic contraction but nifedipine (100 nM) did not. Acetylcholine dose-dependently increased the formation of . This effect was not observed in the presence of 2 mM EGTA. Both verapamil and TMB-8 significantly inhibited formation induced by 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.
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KEYWORD
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Verapamil, Nifedipine, TMB-8, Phospholipase C, Gastric muscle contraction
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