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KMID : 0811720090130030189
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Korean Journal of Physiology & Pharmacology
2009 Volume.13 No. 3 p.189 ~ p.194
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Forskolin Changes the Relationship between Cytosolic Ca2＋ and Contraction in Guinea Pig Ileum
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Han Koon-Hee
Cheon Gap-Jin
Yeon Dong-Soo
Kwon Seong-Chun
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Abstract
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This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic Ca2＋ level ([Ca2＋]i), and Ca2＋ sensitivity in guinea pig ileum. Forskolin (0.1 nM∼10?M) inhibited high K＋ (25 mM and 40 mM)- or histamine (3?M)-evoked contractions in a concentration- dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high K＋- evoked contractions. Spontaneous changes in [Ca2＋]i and contractions were inhibited by forskolin (1?M) without changing the resting [Ca2＋]i. Forskoln (10?M) inhibited muscle tension more strongly than [Ca2＋]i stimulated by high K＋, and thus shifted the [Ca2＋]i-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1?M) inhibited both [Ca2＋]i and muscle tension without changing the [Ca2＋]i-tension relationship. In ?-toxin-permeabilized tissues, forskolin (10?M) inhibited the 0.3?M Ca2＋-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the Ca2＋-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in Ca2＋ sensitivity of contractile elements in high K＋- stimulated muscle and a decrease in [Ca2＋]i in histamine-stimulated muscle.
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KEYWORD
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Fosrkolin, Cytosolic Ca2＋, Ca2＋ sensitivity, Guinea pig ileum
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