Functional Characterization of Adenosine Receptors and Coupling to ATP-Sensitive K⁺ Channels in Guinea Pig Urinary Bladder Smooth Muscle

Abstract

Although multiple adenosine receptors have been identified, the subtype and underlying mechanisms involved in the relaxation response to adenosine in the urinary bladder remain unclear. The present study investigates changes in the membrane potential, as assessed by fluorescence-based techniques, of bladder smooth muscle cells by adenosine receptor agonists acting via ATP-sensitive potassium (K ATP ) channels. Membrane hyperpolarization evoked by adenosine and various adenosine receptor subtype-selective agonists was attenuated or reversed by the K ATP channel blocker glyburide. Comparison of adenosine receptor agonist potencies eliciting membrane potential effects showed a rank order of potency 5Ј-N-ethylcarboxamido adenosine (NECA; Ϫlog EC 50 ϭ 7.97) ϳ 2-p-(2-carboxethyl)phenethyl-amino-5Ј-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680; 7.65) Ͼ 2-chloro adenosine (5.90) ϳ 2-chloro- Collectively, these studies demonstrate that adenosine-evoked membrane hyperpolarization and relaxation of bladder smooth muscle is mediated by A 2A receptor-mediated activation of K ATP channels via adenylate cyclase and elevation of cAMP.

ADP‐induced bladder contractility is mediated by P2Y 12 receptor and temporally regulated by ectonucleotidases and adenosine signaling

“…It has been convincingly shown in this study that adenosine receptors are involved in the regulation of BSM contractility. Adenosine A 2a and A 2b receptors have been suggested to mediate BSM relaxation in previous reports, although the exact receptor type and the signaling pathways are not fully known (8,9). A 2a /A 2b receptors are usually coupled to G s protein, which, on activation, will increase adenylyl cyclase activity.…”

A2A Adenosine Receptor Deficiency Leads to Impaired Tracheal Relaxation via NADPH Oxidase Pathway in Allergic Mice

“…Thus, the biochemical basis of bronchial hyper-reactivity and bronchoconstriction in asthma remains only partially understood. shown the involvement of A 2A AR in smooth muscle relaxation from different organs via the cAMP-PKA pathway (Cushing et al, 1991;Haynes, 2000;Gopalakrishnan et al, 2002;Radenković et al, 2005), but this is the first study to show its involvement in tracheal smooth muscle relaxation. A 2A WT sensitized and A 2A KO control had decreased cAMP and p-PKA levels, thus suggesting that the deficiency of A 2A AR leads to decreased tracheal relaxation due to altered cAMP-PKA signaling.…”

“…Phosphorylation of these proteins results in smooth muscle relaxation through effects on potassium and calcium channels, sodium/potassium ATPases, and calcium sensitivity of myosin (Shore and Moore, 2003). A 2A AR-mediated relaxation via cAMP-PKA has been reported in smooth muscle from various organs (Gopalakrishnan et al, 2002;Huang et al, 2003;Radenković et al, 2005).…”

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

“…Bladder spontaneous activity, an intrinsic feature of bladder smooth muscle tissue is significantly increased in SCI rats, and is the ex vivo correlate of detrusor overactivity. Signaling via A 1 , A 2A and A 2B receptors has been implicated in central and local modulation of normal and pathological bladder activity [24,[73][74][75][76][77]. Our group recently identified a new role for the A 2B adenosine receptor subtype in mediating the ability of inosine to decrease bladder spontaneous activity in SCI rats [24].…”