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

Mahreen Pakzad, Youko Ikeda, Carly McCarthy, Darryl Kitney, Rita Jabr, Christopher Fry*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

11 Citations (Scopus)
289 Downloads (Pure)

Abstract

Purpose. 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.
Methods. 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.
Results. 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 (2-40 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-ethylcarboxamidoadenosine (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.
Conclusions. 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.
Original languageEnglish
Pages (from-to)921-929
Number of pages9
JournalNaunyn-Schmiedeberg's Archives in Pharmacology
Volume389
Issue number8
DOIs
Publication statusPublished - 17 May 2016

Bibliographical note

26 April 2016

Keywords

  • Adenosine
  • adenosine receptor
  • contraction
  • detrusor
  • neuropathic bladder

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