Forskolin Changes the Relationship between Cytosolic Ca and Contraction in Guinea Pig Ileum.
This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic Ca(2+) level ([Ca(2+)](i)), and Ca(2+) sensitivity in guinea pig ileum. Forskolin (0.1 nM~10 microM) inhibited high K(+) (25 mM and 40 mM)- or histamine (3 microM)-evoked contractions in a concentration-dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high K(+)-evoked contractions. Spontaneous changes in [Ca(2+)](i) and contractions were inhibited by forskolin (1 microM) without changing the resting [Ca(2+)](i). Forskoln (10 microM) inhibited muscle tension more strongly than [Ca(2+)](i) stimulated by high K(+), and thus shifted the [Ca(2+)](i)-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1 microM) inhibited both [Ca(2+)](i) and muscle tension without changing the [Ca(2+)](i)-tension relationship. In alpha-toxin-permeabilized tissues, forskolin (10 microM) inhibited the 0.3 microM Ca(2+)-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the Ca(2+)-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in Ca(2+) sensitivity of contractile elements in high K(+)-stimulated muscle and a decrease in [Ca(2+)](i) in histamine-stimulated muscle.
Han
Koon Hee
KH
Department of Internal Medicine, Gangnung Asan Hospital, Gangnung 210-711, Korea.
Cheon
Gap Jin
GJ
Yeon
Dong Soo
DS
Kwon
Seong Chun
SC