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Characterisation of nerve-mediated ATP release from bladder detrusor muscle and its pathological implications.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2019 Dec; Vol. 176 (24), pp. 4720-4730. Date of Electronic Publication: 2019 Nov 03. - Publication Year :
- 2019
-
Abstract
- Background and Purpose: This study aims to characterise the molecular mechanisms that determine variability of atropine resistance of nerve-mediated contractions in human and guinea pig detrusor smooth muscle.<br />Experimental Approach: Atropine resistance of nerve-mediated contractions and the role of P2X1 receptors, were assessed 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.<br />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-diphosphohydrolase 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 enzymic 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 of 1-16 Hz.<br />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 with ACh, implying different routes for their release.<br /> (© 2019 The British Pharmacological Society.)
- Subjects :
- Animals
Atropine pharmacology
Electric Stimulation
Guinea Pigs
Humans
In Vitro Techniques
Muscle, Smooth drug effects
Muscle, Smooth metabolism
Receptors, Purinergic P2X1 metabolism
Species Specificity
Urinary Bladder drug effects
Urinary Bladder metabolism
Adenosine Triphosphatases metabolism
Adenosine Triphosphate metabolism
Muscle Contraction drug effects
Muscle, Smooth physiology
Urinary Bladder physiology
Urinary Bladder, Overactive metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 176
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31430833
- Full Text :
- https://doi.org/10.1111/bph.14840