Relaxing and metabolic inhibitory action of X537A (Lasalocid) on the taenia of the guinea‐pig caecum.

Abstract

SUMMARY1. In the isolated guinea-pig taenia, application of X537A to the muscle caused a relaxation, while A23187 caused a sustained contraction.2. Treatment with adrenergic blocking agents and tetrodotoxin had no effect on the relaxing response to X537A.3. In the presence of a low concentration (10-6 M) of X537A or under hypoxic conditions (bubbled with 95 % N2: 5 % C02), the taenia lost the ability to respond to a high concentration (40 mM) of potassium with a sustained tonic contraction, although the rapid phasic contraction was still present. 4. When a low concentration of X537A was applied the shape of the contractile response to A23187 was changed from a sustained development of tension to an oscillatory tension which was also observed under hypoxia.5. In tissues treated with glycerol for 3 weeks, neither X537A nor A23187 had any effect on the contractile response induced by elevation of calcium concentration (pCa = 4) in the presence of magnesium and ATP.6. Exposure to a low concentration (10-6 M) of X537A, or hypoxia, slightly yet significantly decreased the ATP content of the muscle. A high concentration (10-5 M) of X537A markedly decreased the ATP content to about half normal. A23187 did not alter the ATP content.7. Application of X537A did not alter the calcium content of the muscle and inhibited the A23187-induced increase in content. Under hypoxia, A23187 failed to increase the calcium content of the muscle.8. The results indicate that, in contrast to A23187, X537A has a relaxing and metabolic inhibitory action on the guinea-pig taenia. The action of low concentrations of X537A resembled that of the hypoxia, indicating that X537A might exert its relaxing action, at least in part, by inhibition of aerobic energy metabolism of the muscle.

Studies on the biphasic nature of urinary bladder contraction and function

“…This is indicated by the studies which demonstrate that in the presence of anoxia, both the peak response to bethanechol and the intracellular concentration of ATP decrease over the same time course. These results are similar to those reported by Ishida and Shibata [1982] and Ishida et al [1984] on guinea-pig taenia of the caecum. These investigators demonstrated that the sustained effect of KC1 was lost during hypoxia, whereas the magnitude of the initial phasic contraction decreased in proportion to the concentration of intracellular ATP.…”

Consequences of metabolic inhibition in smooth muscle isolated from guinea‐pig stomach

“…Tissue extracts were made by homogenizing with 6% perchloric acid solution after freezing , or by boiling (Ishida & Shibata, 1982). The smooth muscle tissue (100-150 mg) was incubated in 'normal' solution (see Solutions and chemicals) for 1 h before extraction.…”

Potassium-induced contraction in smooth muscle.

“…Substitution of Cl by other anions like Br, NO3, I or SCN potentiates the K-induced initial transient contraction, whereas the same substitution inhibits the following sustained contraction (Urakawa et al, 1967). Only an initial transient contraction is induced by high K (and also by carbachol) in the presence of Ca antagonists like verapamil (Riemer et al, 1974;Karaki et al, 1984), D600 (Brading & Sneddon, 1980), ruthenium red (Kawamura & Yabu, 1978), cyproheptadine (Lowe et al, 1981) and N2-dansyl-L-arginine-4-t-butylpiperidine amide (TI 233) (Karaki et al, 1983c), inhibitors of aerobic metabolism (Pfaffman et al, 1965;Ferrari & Carpenedo, 1968 ;Tsuda et al, 1977;Nakagawa et al, 1984), inhibitors of the Na pump like ouabain (Pfaffman et al, 1965;Kishimoto & Urakawa, 1982a), Li substitution for Na (Pfaffman et al, 1965;Kishimoto & Urakawa, 1982a), and ionophores with mitochondrial inhibiting action like monensin and X-537A (Ishida & Shibata, 1982;Murakami et al, 1983). The initial transient contraction induced by high K in taenia coli coinsides with a burst of spike discharges (Shimo & Holland, 1966).…”