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KCI등재 학술저널

Forskolin Changes the Relationship between Cytosolic Ca<SUP>2+</SUP> and Contraction in Guinea Pig Ileum

Forskolin Changes the Relationship between Cytosolic Ca<SUP>2+</SUP> and Contraction in Guinea Pig Ileum

This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic Ca<sup>2+</sup> level ([Ca<sup>2+</sup>]<sub>i</sub>), and Ca<sup>2+</sup> sensitivity in guinea pig ileum. Forskolin (0.1 nM∼10&#1356;M) inhibited high K<sup>+</sup> (25 mM and 40 mM)- or histamine (3&#1356;M)-evoked contractions in a concentration- dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high K<sup>+</sup>- evoked contractions. Spontaneous changes in [Ca<sup>2+</sup>]<sub>i</sub> and contractions were inhibited by forskolin (1&#1356;M) without changing the resting [Ca<sup>2+</sup>]<sub>i</sub>. Forskoln (10&#1356;M) inhibited muscle tension more strongly than [Ca<sup>2+</sup>]<sub>i</sub> stimulated by high K<sup>+</sup>, and thus shifted the [Ca<sup>2+</sup>]<sub>i</sub>-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1&#1356;M) inhibited both [Ca<sup>2+</sup>]<sub>i</sub> and muscle tension without changing the [Ca<sup>2+</sup>]<sub>i</sub>-tension relationship. In &#1345;-toxin-permeabilized tissues, forskolin (10&#1356;M) inhibited the 0.3&#1356;M Ca<sup>2+</sup>-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the Ca<sup>2+</sup>-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in Ca<sup>2+</sup> sensitivity of contractile elements in high K<sup>+</sup>- stimulated muscle and a decrease in [Ca<sup>2+</sup>]<sub>i</sub> in histamine-stimulated muscle.

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