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Expression of PDE5 and its stimulation by cGMP‐dependent protein kinase (PKG) determine the magnitude of smooth muscle relaxation in different regions of the stomach
Author(s) -
AlShboul Othman,
Mahavadi Sunila,
Grider John R,
Murthy Karnam S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1008.4
Subject(s) - stomach , stimulation , tonic (physiology) , endocrinology , medicine , myocyte , chemistry , protein kinase a , cgmp dependent protein kinase , muscle contraction , phosphorylation , biology , anatomy , biochemistry , cyclin dependent kinase 2
The contractile phenotypes of proximal and distal gastric smooth muscle are distinct with proximal smooth muscle exhibiting tonic characteristics and distal smooth muscle phasic characteristics. In smooth muscle, the main cGMP hydrolyzing enzyme phosphodiesterase 5 (PDE5) plays an important role in determining the strength and duration of cGMP signaling, and thus muscle relaxation. The activity of PDE5 is stimulated by phosphorylation via PKG. Aim To determine the expression and regulation of PDE5 activity in proximal versus distal regions of the stomach. Methods Expression of PDE5 and PKG‐mediated phosphorylation of PDE5 at Ser 92 were measured by western blot. PDE5 activity was measured using [ 3 H]cGMP and cGMP‐mediated relaxation was measured by scanning micrometry. Results Muscle cells from proximal stomach contained 2 times more PDE5 than muscle cells from distal stomach. Activation of PKG by the NO‐donor caused an increase in PDE5 phosphorylation and activity, but the responses were higher in muscle cells from proximal stomach. In contrast, muscle relaxation was greater in muscle cells from distal stomach consistent with the lower amounts of PDE5 in muscle cells from this region. Conclusion . Higher expression of PDE5 and greater PKG‐mediated augmentation of PDE5 activity in muscle cells from proximal stomach correlate with the tonic phenotype of muscle in proximal stomach relative to distal stomach.