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Diabetes‐induced colonic slow transit mediated by the up‐regulation of PDGFRα + cells/SK3 in streptozotocin‐induced diabetic mice
Author(s) -
Song N.N.,
Lu H.L.,
Lu C.,
Tong L.,
Huang S.Q.,
Huang X.,
Chen J.,
Kim Y.C.,
Xu W.X.
Publication year - 2018
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13326
Subject(s) - streptozotocin , apamin , interstitial cell of cajal , endocrinology , medicine , agonist , receptor , diabetes mellitus , potassium channel , immunohistochemistry
Background A major complication related to gastrointestinal ( GI ) symptoms in diabetic patients is chronic constipation. Constipation has serious negative impacts on quality of life; however, without a comprehensive understanding of the disease, currently available treatments cannot provide a cure. Platelet‐derived growth factor receptor alpha‐positive cells ( PDGFR α + cells), which form the SIP syncytium with interstitial cells of Cajal and smooth muscle cells, play important roles in GI motility. In the present study, the contributions of PDGFR α + cells to diabetes‐induced colonic slow transit were investigated in streptozotocin ( STZ )‐induced diabetic mice. Methods Western blotting, quantitative PCR , contractile experiments, and intracellular recording were used in the present study. Key Results The results demonstrated that the colon length was increased in STZ ‐treated mice. The colonic transit of artificial fecal pellets in vitro was significantly delayed in STZ ‐treated mice. The mRNA and protein expression of PDGFR α, small‐conductance Ca 2+ ‐activated K channels ( SK 3), and P2Y1 receptors were increased in the colons of STZ ‐treated mice. In contractile experiments, the colonic smooth muscles were more sensitive to the SK 3 agonist and antagonist (Cy PPA and apamin) and the P2Y1 agonist and antagonist ( MRS 2365 and MRS 2500) in STZ ‐treated mice. Intracellular recordings showed the responses of membrane potentials in colonic smooth muscle cells to Cy PPA , apamin, MRS 2365, and MRS 2500 were more sensitive in STZ ‐treated mice. The electric field stimulation‐induced P2Y1/ SK 3‐dependent fast inhibitory junctional potentials ( fIJP s) of colonic smooth muscles were more significantly hyperpolarized in STZ ‐treated mice. Conclusions and Inferences These results suggest that the purinergic neurotransmitters/P2Y1/ SK 3 signaling pathway is up‐regulated in the diabetic colons, thereby mediating diabetes‐induced colonic slow transit.