Purinergic signalling in the urinary bladder – When function becomes dysfunction

Fry, Christopher; McCloskey, Karen

doi:10.1016/j.autneu.2021.102852

Cited by 8 publications

(1 citation statement)

References 165 publications

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“…It is generally presumed that (i) distention of the bladder wall during filling increases sensory nerve activity [ 26 , 27 ], (ii) the bladder mucosa secretes ATP in response to physical and chemical stimuli [ 2 , 23 , 28 ] and (iii) the activation of afferent nerves in LP and urothelium by extracellular ATP initiates voiding [ 1 ]. Therefore, ATP is believed to play a significant sensory role in the control of normal micturition [ 29 ]. In addition, bladder excitability disorders may also be associated with aberrant purinergic signaling since increased intraluminal levels of ATP are found in patients with overactive bladder syndrome [ 10 , 30 ], interstitial cystitis and bladder pain syndrome [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria

Branco

Cruz

Peikani

et al. 2023

IJMS

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The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N6-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling.

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