title: The inhibitory effect of tiamulin on high K(+)-induced contraction in guinea pig intestinal smooth muscle.
abstract: Tiamulin with an IC50 of 1.7 x 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 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 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 x 10(-7)-2 x 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 Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.
authors.affiliation: Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakajyo
authors.forename: T
authors.initials: T
authors.lastname: Fukui
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: N
authors.initials: N
authors.lastname: Urakawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D007422:Intestines / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015220:Calcium Channels; D004224:Diterpenes; D014700:Verapamil; C014224:tiamulin; D011188:Potassium; D002118:Calcium