title: Acid and stretch, but not capsaicin, are effective stimuli for ATP release in the porcine bladder mucosa: Are ASIC and TRPV1 receptors involved?
abstract: Stretch-evoked ATP release from the bladder mucosa is a key event in signaling bladder fullness. Our aim was to examine whether acid and capsaicin can also release ATP and to determine the receptors involved, using agonists and antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine bladder mucosa were exposed to acid, capsaicin or stretch. Strip tension was monitored. Bath fluid was collected for ATP measurement. Gene expression of ASICs and TRPV1 in porcine bladders was quantified using quantitative real-time PCR (qRT-PCR). Stretch stimulus (150% of original length) repeatedly and significantly increased ATP release to approximately 45 times basal release. Acid (pH 6.5, 6.0, 5.6) contracted mucosal strips and also increased ATP release up to 30-fold, without evidence of desensitization. Amiloride (0.3 μM) reduced the acid-evoked ATP release by approximately 70%, while capsazepine (10 μM) reduced acid-evoked ATP release at pH 6.0 and pH 5.6 (by 68% and 61%, respectively). Capsaicin (0.1-10 μM) was ineffective in causing ATP release, and also failed to contract porcine mucosal or detrusor strips. Gene expression for ASIC1, ASIC2, ASIC3 and TRPV1 was seen in the lateral wall, dome, trigone and neck of both detrusor and mucosa. In conclusion, stretch and acid induce ATP release in the porcine bladder mucosa, but capsaicin is ineffective. The pig bladder is a well-known model for the human bladder, however these data suggest that it should be used with caution, particularly for TRPV1 related studies.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Prajni.sadananda@bristol.ac.uk
authors.forename: Prajni
authors.initials: P
authors.lastname: Sadananda
authors.forename: Felicity C L
authors.initials: FC
authors.lastname: Kao
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Mansfield
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Burcher
mesh_terms: D062565:Acid Sensing Ion Channels; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010812:Physical Stimulation; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D062687:Sodium Channel Agonists; D015222:Sodium Channels / Q000378:metabolism*; D034421:Sus scrofa; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
chemical_list: C568266:ASIC1 protein, human; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D049990:Membrane Transport Modulators; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D062687:Sodium Channel Agonists; D015222:Sodium Channels; D050916:TRPV Cation Channels; D000255:Adenosine Triphosphate; D002211:Capsaicin