By measuring the isometric tension produced by thin strips of taenia coli smooth muscle, inhibitory effects of caffeine on the acetylcholine (ACh)-induced phasic contraction were examined under the high-K depolarized state. Caffeine (2mM) inhibited ACh-contraction by three different mechanisms: 1) by decreasing the efficiency of Ca-release from Ca-store, 2) by inhibiting the loading of Ca-store with Ca
2+ and 3) by accelerating the depletion of Ca-store. In the presence of physiological concentration of Ca
2+ the first mechanism was found to be dominant with a slight contribution of the second. Under the nominally Ca-free conditions the contribution of the third was also important.
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