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

Abstract

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.