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UROTHELIAL EPAC: NOVEL MEDIATOR IN THE REGULATION OF BLADDER CAPACITY
Author(s) -
Nakagomi Hiroshi,
Kullmann F Aura,
Ruiz Wily,
WolfJohnston Amanda,
Apodaca Gerard,
Birder Lori
Publication year - 2015
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.29.1_supplement.666.18
Subject(s) - exocytosis , microbiology and biotechnology , agonist , urothelium , chemistry , medicine , endocrinology , secretion , protein kinase a , biophysics , receptor , urinary bladder , kinase , biology , biochemistry
Bladder filling elicits exocytosis and vesicle fusion increasing the apical surface area of epithelial cells (measured by membrane capacitance). One stimulus governing apical exocytosis is cAMP. Although initially the effects of cAMP were solely attributed to activation of protein kinase A (PKA), recent findings uncovered a novel c‐AMP sensor, EPAC (exchange protein directly activated by cAMP). This protein plays a critical role in calcium handling and ion transport, vesicle trafficking and secretion, and barrier function in various organs. Here we investigated the expression and role of EPAC in signaling apical membrane dynamics. Bladders from female Sprague Dawley rats and New Zealand white rabbits were used for western blot and immunohistochemistry or for culturing urothelial cells for fura‐2 calcium imaging and ATP release. Transepithelial capacitance was measured by placing bladder mucosa in modified Ussing chambers and increasing hydrostatic pressure to mimic bladder filling (in the presence or the absence of EPAC agonist‐ 8‐pCPT, or antagonist‐ ESI‐09). EPAC was expressed in the urothelium, however the agonist did not alter Ca 2+ nor ATP release in cultured cells. Nevertheless, the EPAC agonist (used in rabbit UT) significantly increased transepithelial capacitance (30% vs 7% in control) in the absence of stretch; stretch‐induced capacitance was reduced by the EPAC antagonist. Our results indicate that EPAC plays an important role in augmenting bladder filling induced increases in urothelial surface area. The lack of ATP involvement suggests that EPAC mediated pathways could lead to increasing bladder capacity without affecting underlying bladder nerves.