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 |
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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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