期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 285, 期 3, 页码 F423-F429出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00056.2003
关键词
mechanosensitivity; urinary bladder; inositol 1,4,5-triphosphate-sensitive pathways; exocytosis
资金
- NIDDK NIH HHS [R01-DK-47938, R01-DK-54824, R01-DK-57284] Funding Source: Medline
- NINDS NIH HHS [R01-NS-045078] Funding Source: Medline
ATP can be released from a variety of cell types by mechanical stimulation; however, the mechanism for this release and the influence of pathology are not well understood. The present study examined intracellular signaling mechanisms involved in swelling-evoked (exposure to a hypotonic solution) release of ATP in urothelial cells from normal cats and cats diagnosed with interstitial cystitis (feline interstitial cystitis; FIC). Using the luciferin-luciferase bioluminescent assay, we demonstrate that swelling-evoked ATP release is significantly elevated in FIC cells. In both normal and FIC cells, ATP release was significantly decreased (mean 70% decrease) by application of blockers of stretch-activated channels (amiloride or gadolinium), as well as brefeldin A and monensin (mean 90% decrease), suggesting that ATP release occurs when ATP-containing vesicles fuse with the plasma membrane. Swelling-evoked release was reduced after removal of external calcium (65%), and release was blocked by incubation with BAPTA-AM or agents that interfere with internal calcium stores (caffeine, ryanodine, heparin, or 2-aminoethoxydiphenyl borate). In addition, agents known to act through inositol 1,4,5-triphosphate (IP(3)) receptors (thapsigargin, acetylcholine) release significantly more ATP in FIC compared with normal urothelium. Taken together, these results suggest that FIC results in a novel hypersensitivity to mechanical stimuli that may involve alterations in IP(3)-sensitive pathways.
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