Clinically, methylxanthines are known to be potent bronchodilators. However, methylxanthines induce contraction for many types of smooth muscle. To clarify this inconsistency, we investigated the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and tension in porcine bronchial smooth muscle.
Porcine bronchial muscle rings were loaded with a Ca2+ indicator dye, Fura-2/AM. The light emission ratio (R340/380) of Fura-2 was recorded to estimate the change in [Ca2+]i, and the isometric tension was simultaneously measured with a force displacement transducer. At the beginning of each experiment, changes in muscle tension and [Ca2+]i induced by 90mM KCl were recorded as control values (100%). Thereafter, tension and [Ca2+]i were recorded under the following conditions: changes induced by histamine (10-6~10-4M), by 90mM KCl or 0.1mM histamine in a Ca2+-free medium, by 2.5mM caffeine, and by 90mM KCl and 0.1mM histamine in the presence of 2.5mM caffeine. Histamine (10-6~10-4M) induced concentration-dependent increases in tension and [Ca2+]i. In the Ca2+-free medium, the increases in tension and [Ca2+]i induced by 90mM KCl were significantly reduced, but those induced by histamine were not. Caffeine itself caused transient increases in tension and [Ca2+]i. Caffeine Suppressed the increases tension induced by histamine, but it did not suppress the increases [Ca2+]i induced by histamine. Caffeine did not affect the increases tension and [Ca2+]i induced by 90mM KCl. Our data suggest that the increases tension induced by histamine is mainly caused by the release of stored Ca2+ and that induced by high K+ is dependent on extracellular Ca2+. Caffeine induces contraction and increase in [Ca2+]i in porcine bronchial muscle. However, caffeine suppresses the histamine-induced tension by inhibiting the histamine-induced augmentation of Ca2+ sensitivity of the contractile proteins.
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