Characterisation of nerve‐mediated ATP release from bladder detrusor muscle and its pathological implications

Carly J McCarthy, Youko Ikeda, Deborah Skennerton, Basu Chakrabarty, Anthony J Kanai, Rita I Jabr, Christopher H Fry

Research output: Contribution to journalArticle (Academic Journal)

1 Citation (Scopus)
9 Downloads (Pure)

Abstract

BACKGROUND AND PURPOSE

To characterise the molecular mechanisms that determine variability of atropine-resistance of nerve-mediated contractions in human and guinea-pig detrusor smooth muscle 

EXPERIMENTAL APPROACH

Atropine-resistance of nerve-mediated contractions, and the role of P2X1 receptors, was measured in isolated preparations from guinea-pigs and also humans with or without overactive bladder syndrome, from which the mucosa was removed. Nerve-mediated ATP release was measured directly with amperometric ATP-sensitive electrodes. Ecto-ATPase activity of guinea-pig and human detrusor samples was measured in vitro by measuring the concentration-dependent rate of ATP breakdown. The transcription of ecto-ATPase subtypes in human samples was measured by qPCR.

KEY RESULTS

Atropine resistance was greatest in guinea-pig detrusor, absent in human tissue from normally-functioning bladders and intermediate in human overactive bladder. Greater atropine resistance correlated with reduction of contractions by the ATP-diphospho-hydrolase apyrase, directly implicating ATP in their generation. E-NTPDase-1 was the most abundantly transcribed ecto-ATPase of those tested and transcription was reduced in tissue from human overactive, compared to normal, bladders. E-NTPDase-1 enzymatic activity was inversely related to the magnitude of atropine resistance. Nerve-mediated ATP release was continually measured and varied with stimulation frequency over the range 1-16 Hz.

CONCLUSION AND IMPLICATIONS

Atropine-resistance in nerve-mediated detrusor contractions is due to ATP release and its magnitude is inversely related to E-NTPDase-1 activity. ATP is released under different stimulation conditions compared to acetylcholine that implies different routes for their release.

Original languageEnglish
Number of pages11
JournalBritish Journal of Pharmacology
Early online date20 Aug 2019
DOIs
Publication statusE-pub ahead of print - 20 Aug 2019

Fingerprint Dive into the research topics of 'Characterisation of nerve‐mediated ATP release from bladder detrusor muscle and its pathological implications'. Together they form a unique fingerprint.

  • Cite this