Long-lasting contractile action and the inhibitory action of cupric ions on ileal longitudinal muscle.
Cupric ions (Cu(2+)), at concentrations above 0.03 mM, induced a progressive increase in the tonic contraction of guinea-pig ileal longitudinal muscle. Maximal contraction of 0.1 mM Cu(2+) attained a level above that of the 60-mM K(+)-induced tonic response, within 20 min of application. The tension induced by Cu(2+) persisted for more than several hours. Tetrodotoxin (3 x 10(-6) M) had no effect on the contraction induced by 0.1 mM Cu(2+). After incubation in a Ca(2+)-free medium, the ileal response to 0.1 mM Cu(2+) was lost. Nifedipine, a L-type Ca(2+) channel blocker, dose-dependently inhibited contractions induced by Cu(2+). As the duration of the first application of 0.1 mM Cu(2+) increased above 30 min, after washing with normal medium, the contractile response to a second application of 0.1 mM Cu(2+) decreased gradually. After 150 min of the first application of 0.1 mM Cu(2+), a second application of Cu(2+) could not evoke any contraction. After the application of 0.1 mM Cu(2+) for 150 min, when muscles were washed with a medium containing 1 mM EDTA, the response to 0.1 mM Cu(2+) returned to a greater extent in the normal Ca(2+) medium. In conclusion, Cu(2+) (0.1 mM) induced a maximal ileal tension above that of the K-induced tonic response within 20 min. The ileal contraction to Cu(2+) persisted for more than several hours and depended on extracellular Ca(2+) concentrations. It is possible that a part of Cu(2+), bound to a EDTA-inaccessible site, also has a tension inhibitory effect.
Miyazaki
K
K
Department of Veterinary Pharmacology, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753, Japan.
Nasu
T
T
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D015203:Reproducibility of Results; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D013779:Tetrodotoxin; D003300:Copper; D004492:Edetic Acid; D009543:Nifedipine; D002118:Calcium