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
- Koon Hee Han Gap Jin Cheon Dong Soo Yeon Seong Chun Kwon
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제13권 제3호
- 등재여부 : KCI등재
- 2009.01
- 189 - 194 (6 pages)
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∼10ՌM) inhibited high K<sup>+</sup> (25 mM and 40 mM)- or histamine (3ՌM)-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 (1ՌM) without changing the resting [Ca<sup>2+</sup>]<sub>i</sub>. Forskoln (10ՌM) 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 (1ՌM) 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 Ձ-toxin-permeabilized tissues, forskolin (10ՌM) inhibited the 0.3ՌM 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.