title: Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders.
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-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. 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.
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK.
authors.forename: Mahreen
authors.initials: M
authors.lastname: Pakzad
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK.
authors.forename: Youko
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK.
authors.forename: Carly
authors.initials: C
authors.lastname: McCarthy
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK.|School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
authors.forename: Darryl G
authors.initials: DG
authors.lastname: Kitney
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK.|Department of Biochemistry & Physiology, University of Surrey, Surrey, UK.
authors.forename: Rita I
authors.initials: RI
authors.lastname: Jabr
authors.affiliation: Departments of Urology and Surgical Sciences, University College London, London, UK. chris.fry@bristol.ac.uk.|School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK. chris.fry@bristol.ac.uk.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Fry
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D001750:Urinary Bladder, Neurogenic / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D008024:Ligands; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1
keywords: Adenosine; adenosine receptor; contraction; detrusor; neuropathic bladder