EP3 activation facilitates bladder excitability via HCN channels on ICCs

Autor: Xiaoyang Hu, Qian Liu, Teng Zhang, Jingzhen Zhu, Qingqing Wang, Xingyou Dong, Longkun Li, Chao Wu, Zhenxing Yang
Rok vydání: 2017
Předmět:
0301 basic medicine
Agonist
medicine.drug_class
Blotting
Western
Urinary Bladder
Biophysics
Inflammation
Pharmacology
urologic and male genital diseases
Biochemistry
Dinoprostone
Rats
Sprague-Dawley
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Western blot
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
medicine
Animals
Patch clamp
Prostaglandin E2
Receptor
Molecular Biology
Cells
Cultured
Mice
Knockout
Microscopy
Confocal
medicine.diagnostic_test
Chemistry
Antagonist
Cell Biology
Anatomy
Interstitial Cells of Cajal
female genital diseases and pregnancy complications
Interstitial cell of Cajal
Mice
Inbred C57BL
Pyrimidines
030104 developmental biology
Receptors
Prostaglandin E
EP3 Subtype
symbols
Calcium
Female
lipids (amino acids
peptides
and proteins)
medicine.symptom
030217 neurology & neurosurgery
Muscle Contraction
Protein Binding
medicine.drug
Zdroj: Biochemical and Biophysical Research Communications. 485:535-541
ISSN: 0006-291X
Popis: EP3 is a receptor for prostaglandin E2 (PGE2), and although its effect on bladder excitability has attracted considerable attention, the underlying mechanism remains unclear. To investigate whether the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the interstitial cells of Cajal (ICCs) of the bladder are involved in the effect of EP3 activation on bladder excitability, wild-type mice, HCN1 knockout (HCN1-/-) mice and rats were used in our study. Double immunofluorescence staining and immunoprecipitation assays demonstrated the interaction between EP3 and the HCN channels. Sulprostone is a selective agonist of EP3. The current density of HCN channels was enhanced by sulprostone or PGE2 using whole-cell patch clamping. Western blot analyses showed that the expression levels of HCN1 and HCN4 were higher in bladders that had undergone intravesical instillation with sulprostone than in bladders treated with normal saline (NS). Both PGE2 and sulprostone increased the calcium concentration of the ICCs, and their effects were inhibited by ZD7288 (antagonist of HCN channels) treatment. In bladder detrusor strip testing, both PGE2 and sulprostone enhanced the amplitude of the bladder detrusor in HCN1-/- mice; however, these effects were less than those in the wild-type mice. Furthermore, the effects of PGE2 and sulprostone were inhibited by ZD7288. Taken together, our results indicate that EP3 is expressed in bladder ICCs and facilitates bladder excitability via HCN channels. This study provides more comprehensive insights into the mechanism between inflammation and bladder excitability and highlights methods that can resolve bladder hyperactivity.
Databáze: OpenAIRE
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