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Characterisation of nerve‐mediated ATP release from detrusor muscle; pathological implications

McCarthy, Carly J., Ikeda, Youko, Skennerton, Deborah, Chakrabarty, Basu, Kanai, Anthony J., Jabr, Rita I. and Fry, Christopher H. (2019) Characterisation of nerve‐mediated ATP release from detrusor muscle; pathological implications British Journal of Pharmacology.

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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

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
McCarthy, Carly J.
Ikeda, Youko
Skennerton, Deborah
Chakrabarty, Basu
Kanai, Anthony J.
Jabr, Rita I.rita.jabr@surrey.ac.uk
Fry, Christopher H.
Date : 20 August 2019
Funders : National Institutes of Health, St Peter's Trust for kidney, bladder and prostate research, University College London
DOI : 10.1111/bph.14840
Copyright Disclaimer : © 2019 The British Pharmacological Society
Uncontrolled Keywords : Detrusor smooth muscle; atropine resistance; ATP release; Ecto‐ATPase activity
Depositing User : Clive Harris
Date Deposited : 30 Sep 2019 10:00
Last Modified : 15 Nov 2019 13:21
URI: http://epubs.surrey.ac.uk/id/eprint/852831

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