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Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders

Pakzad, M, Ikeda, Y, McCarthy, C, Kitney, DG, Jabr, Rita and Fry, Christopher (2016) Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders Naunyn-Schmiedeberg's Archives of Pharmacology, 389 (8). pp. 921-929.

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Abstract

To measure the relative transcription of adenosine receptor subtypes and the contractile effects of adenosine and selective receptor-subtype ligands on detrusor smooth muscle from patients with neuropathic overactive (NDO) and stable bladders and also from guinea-pigs. Contractile function was measured at 37°C in vitro from detrusor smooth muscle strips. Contractions were elicited by superfusate agonists or by electrical field stimulation. Adenosine-receptor (A1, A2A, A2B, A3) transcription was measured by RT-PCR. Adenosine attenuated nerve-mediated responses with equivalent efficacy in human and guinea-pig tissue (pIC50 3.65–3.86); the action was more effective at low (1–8 Hz) compared to high (20– 40 Hz) stimulation frequencies in human NDO and guinea-pig tissue. With guinea-pig detrusor the action of adenosine was mirrored by the A1/A2-agonist N-ethylcarboxamido adenosine (NECA), partly abolished in turn by the A2B-selectve antagonist alloxazine, as well as the A1-selective agonist N6- cyclopentyladenosine (CPA). With detrusor from stable human bladders the effects of NECA and CPA were much smaller than that of adenosine. Adenosine also attenuated carbachol contractures, but mirrored by NECA (in turn blocked by alloxazine) only in guinea-pig tissue. Adenosine receptor subtype transcription was measured in human detrusor and was similar in both groups, except reduced A2A levels in overactive bladder. Suppression of the carbachol contracture in human detrusor is independent of A-receptor activation, in contrast to an A2B-dependent action with guinea-pig tissue. Adenosine also reduced nerve-mediated contractions, by an A1- dependent action suppressing ATP neurotransmitter action.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Pakzad, MUNSPECIFIEDUNSPECIFIED
Ikeda, YUNSPECIFIEDUNSPECIFIED
McCarthy, CUNSPECIFIEDUNSPECIFIED
Kitney, DGUNSPECIFIEDUNSPECIFIED
Jabr, RitaR.Jabr@surrey.ac.ukUNSPECIFIED
Fry, ChristopherC.H.Fry@surrey.ac.ukUNSPECIFIED
Date : 17 May 2016
Identification Number : 10.1007/s00210-016-1255-1
Copyright Disclaimer : This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Uncontrolled Keywords : Adenosine . neuropathic bladder . detrusor . contraction . adenosine receptor
Depositing User : Symplectic Elements
Date Deposited : 09 Sep 2016 10:06
Last Modified : 04 Aug 2017 17:35
URI: http://epubs.surrey.ac.uk/id/eprint/812066

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