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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00210-016-1255-1) contains supplementary material, which is available to authorized users.

Aims To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. Methods Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0, respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. Results Values of vCE, but not P0, diminished with age in female subjects. vCE was most significantly associated with the 20–80% duration of isovolumetric contraction t20–80;and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20–80 and isovolumetric pressure indices. Conclusions The rate of isovolumetric subtracted detrusor pressure (t20–80) increase shows a very significant association with indices of bladder contractility as derived from a derived force–velocity curve. We propose that t20–80 is a detrusor contractility parameter (DCP).

The Detrusor Contractility Parameter (DCP) (t ), can be measured easily from the pressure flow curves of a urodynamic test. The Watts Factor at maximum urine flow, WF , can be readily calculated, but is only applicable to women. In both women and men without a high degree of bladder outlet obstruction, DCP is better associated with true detrusor contractility than any Watts Factor analysis.

Aims Bladder wall stretch increases tissue tension and releases adenosine 5'‐triphosphate (ATP) as part of a transduction process to sense bladder filling. Aging is associated with bladder fibrosis to produce a stiffer bladder wall: this may augment ATP release and contribute to age‐dependent urgency. Muscarinic agonists also release ATP and present a potential target for antimuscarinic agents, but its age‐dependency is unknown. This study aimed, in young and old mice, to: (a) quantify the relationship between bladder wall stiffness and stretch‐dependent ATP release and; (b) characterize muscarinic agonist‐dependent release. Methods ATP release from young (9‐12 weeks) and aged (24 months) mouse bladder wall was measured in vitro, with a luciferin‐luciferase assay, after stretch or carbachol exposure. Bladder wall stiffness, measured simultaneously during stretch, was compared to histological proportions of connective tissue and detrusor muscle. Results With young mice, stretch‐activated ATP release required an intact mucosa and was positively associated with wall stiffness. ATP release by carbachol was about four‐fold greater compared to stretch. With aged mice: ATP release varied a hundred‐fold and no association with stiffness; carbachol release diminished; connective tissue and mucosa thickness increased. Conclusions With young mice, stretch, or muscarinic agonists potently induce bladder wall ATP release. Stretch‐dependent release is proportional to bladder wall stiffness, independent of the extent of stretch. With aged mice dependence of stretch‐activated ATP release with stiffness was lost. The huge variability of release suggests that aged mice do not form a homogenous cohort and may underlie the heterogeneity in bladder filling sensations.