Forskolin Changes the Relationship between Cytosolic Ca2+ and Contraction in Guinea Pig Ileum.
10.4196/kjpp.2009.13.3.189
- Author:
Koon Hee HAN
1
;
Gap Jin CHEON
;
Dong Soo YEON
;
Seong Chun KWON
Author Information
1. Department of Internal Medicine, Gangnung Asan Hospital, Gangnung 210-711, Korea.
- Publication Type:Original Article
- Keywords:
Fosrkolin;
Cytosolic Ca2+;
Ca2+ sensitivity;
Guinea pig ileum
- MeSH:
Animals;
Contracts;
Cytosol;
Forskolin;
Guanosine Triphosphate;
Guinea;
Guinea Pigs;
Histamine;
Ileum;
Muscle Tonus;
Muscle, Smooth;
Muscles
- From:The Korean Journal of Physiology and Pharmacology
2009;13(3):189-194
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 micrometer) inhibited high K+ (25 mM and 40 mM)- or histamine (3 micrometer)-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 micrometer) without changing the resting [Ca2+]i. Forskoln (10 micrometer) 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 micrometer) inhibited both [Ca2+]i and muscle tension without changing the [Ca2+]i-tension relationship. In alpha-toxin-permeabilized tissues, forskolin (10 micrometer) inhibited the 0.3 micrometer 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.
