Tiamulin with an IC
50 of 1.7 × 10
-6 M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K
+ (Hyper 60 K
+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 × 10
-6-2 × 10
-5 M) of the Ca
2+-induced contraction in depolarized muscle was competitively antagonized by raising external Ca
2+. Tiamulin (2 × 10
-5 M) slightly affected the Hyper 60 K
+-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 × 10
-5 M) inhibited the Hyper 60 K
+-induced contraction with decreasing [Ca
2+]
cyt level. Although the inhibitory effect of 10
-7-10
-5 M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K
+-induced contraction was reduced under hypoxia, the effect of tiamulin (2 × 10
-7-2 × 10
-4 M) was not modified. Tiamulin changed neither the intracellular Na
+ and K
+ content of the depolarized muscle nor the Ca
2+-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K
+-induced tonic contraction is possibly due to the competitive inhibition of Ca
2+ entry through the voltage-dependent Ca
2+ channel of the intestinal smooth muscle cell.
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