Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon

Hu,Liu-Dan; Yu,Bao-Ping; Yang,Bin

doi:10.3892/mmr.2012.984

October 2012 Volume 6 Issue 4

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October 2012 Volume 6 Issue 4

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Article

Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon

Authors:
- Liu-Dan Hu
- Bao-Ping Yu
- Bin Yang
View Affiliations / Copyright

Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Pages: 833-837
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Published online on: July 11, 2012

https://doi.org/10.3892/mmr.2012.984
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Abstract

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium current (ICa-L) prior to and following the application of various concentrations of DCA. The application of DCA (10-6-10-4 M) decreased the amplitude of spontaneous contractions of the PCSM strips in a dose-dependent manner. The administration of DCA (10-5 M) caused the relaxation of isolated smooth muscle strips pre-contracted by acetylcholine (Ach) or KCl (by 12.2±1.5 and 16.3±6.9%, respectively). The concentration-response curve of CaCl2 was shifted to the right. Pre-treatment of the strips with the protein kinase C (PKC) inhibitor chelerythrine (1 µM) significantly attenuated the effects of DCA on the strips pre-contracted by Ach. DCA reduced the peak ICa-L by 6.02±0.87% at 10-6 M, 15.02±1.73% at 10-5 M and 47.14±3.79% at 10-4 M. DCA shifted the current-voltage (I-V) curve of ICa-L upward, but the contour of the I-V curve was unchanged, and the peak current-induced voltage remained at 0 mV. Pre-treatment with chelerythrine (1 µM) blocked the actions of DCA on the ICa-L. Taken together, the actions of DCA on ICa-L in rat colonic SMCs contributed to a negative inotropic effect. These actions appear to be mediated through protein kinase C. Furthermore, this study suggests another possible mechanism for the DCA-related modulation of gastrointestinal motility.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon

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