The Inhibitory Effect of Tiamulin on High K+-Induced Contraction in Guinea Pig Intestinal Smooth Muscle.

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Tiamulin with an IC50 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 Ca2+-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. 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 [Ca2+]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 Ca2+-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 Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.
公益社団法人日本薬理学会の論文