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Impaired contractile responses and altered expression and phosphorylation of Ca(2+) sensitization proteins in gastric antrum smooth muscles from ob/ob mice.
- Source :
-
Journal of muscle research and cell motility [J Muscle Res Cell Motil] 2013 May; Vol. 34 (2), pp. 137-49. Date of Electronic Publication: 2013 Apr 11. - Publication Year :
- 2013
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Abstract
- Diabetic gastroparesis is a common complication of diabetes, adversely affecting quality of life with symptoms of abdominal discomfort, nausea, and vomiting. The pathogenesis of this complex disorder is not well understood, involving abnormalities in the extrinsic and enteric nervous systems, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The ob/ob mouse model of obesity and diabetes develops delayed gastric emptying, providing an animal model for investigating how gastric smooth muscle dysfunction contributes to the pathophysiology of diabetic gastroparesis. Although ROCK2, MYPT1, and CPI-17 activities are reduced in intestinal motility disorders, their functioning has not been investigated in diabetic gastroparesis. We hypothesized that reduced expression and phosphorylation of the myosin light chain phosphatase (MLCP) inhibitory proteins MYPT1 and CPI-17 in ob/ob gastric antrum smooth muscles could contribute to the impaired antrum smooth muscle function of diabetic gastroparesis. Spontaneous and carbachol- and high K(+)-evoked contractions of gastric antrum smooth muscles from 7 to 12 week old male ob/ob mice were reduced compared to age- and strain-matched controls. There were no differences in spontaneous and agonist-evoked intracellular Ca(2+) transients and myosin light chain kinase expression. The F-actin:G-actin ratios were similar. Rho kinase 2 (ROCK2) expression was decreased at both ages. Basal and agonist-evoked MYPT1 and myosin light chain 20 phosphorylation, but not CPI-17 phosphorylation, was reduced compared to age-matched controls. These findings suggest that reduced MLCP inhibition due to decreased ROCK2 phosphorylation of MYPT1 in gastric antrum smooth muscles contributes to the antral dysmotility of diabetic gastroparesis.
- Subjects :
- Animals
Gastroparesis metabolism
Gastroparesis pathology
Gastroparesis physiopathology
Intracellular Signaling Peptides and Proteins
Mice
Mice, Obese
Muscle, Smooth pathology
Muscle, Smooth physiopathology
Myosin Light Chains metabolism
Phosphorylation
Pyloric Antrum pathology
Pyloric Antrum physiopathology
Muscle Contraction
Muscle Proteins metabolism
Muscle, Smooth metabolism
Myosin-Light-Chain Kinase metabolism
Myosin-Light-Chain Phosphatase metabolism
Phosphoproteins metabolism
Pyloric Antrum metabolism
rho-Associated Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2657
- Volume :
- 34
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of muscle research and cell motility
- Publication Type :
- Academic Journal
- Accession number :
- 23576331
- Full Text :
- https://doi.org/10.1007/s10974-013-9341-1