The regulation of distention-induced ATP release from urothelium by the adenylyl cyclase-cyclic AMP pathway.
Distention of the bladder during urine storage induces ATP release from urothelium, thereby facilitating transmission of visceral sensory signals to afferent nerve fibers. An excess of urothelial ATP release was found in interstitial cystitis, a condition accompanied by hyperesthesia of the urinary bladder; it remains unclear which signals are involved in this upregulation. The present study demonstrated that the adenylyl cyclase pathway enhances distention-induced ATP release in mouse bladder. In the absence of distention, adenylyl cyclase activation by forskolin or cyclic AMP increases by rolipram did not induce significant ATP release. However, forskolin or rolipram significantly enhanced ATP release from urothelium by a physiologically normal urine storage pressure (5 cmH(2)O). Blockade of adenylyl cyclases did not alter pressure-induced ATP release in normal condition. Thus, the adenylyl cyclase-cAMP pathway might be activated in pathological conditions and cause an excess of ATP release.
Department of Neurophysiology, Akita University Graduate School of Medicine 1-1-1 Hondo, Akita, Akita 010-8543, Japan. kmiyai@med.akita-u.ac.jp
Kazumasa
K
Matsumoto-Miyai
Erika
E
Yamada
Masaru
M
Yoshizumi
Masahito
M
Kawatani
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases