Effect of exogenous adenosine and its monophosphate on the contractile response to acetylcholine in the human isolated detrusor muscle strips

Abstract

1. Adenosine (0.1-1 mM) or its 5'-monophosphate (5'-AMP) induced a concentration-dependent relaxation of tension caused by acetylcholine (0.2 microM) in human urinary bladder detrusor strips. 2. This effect was antagonized concentration dependently by theophylline at an apparent pA2 value of about 5. 3. Maximum relaxation by adenosine or 5'-AMP never exceeded 50% and 80%, respectively, of acetylcholine-induced tension. Relaxation by some beta2-adrenoceptor agonists (0.1-0.2 mM) or norepinephrine was limited to about 50% of maximum. 4. The responses to adenosine and terbutaline were additive, causing full relaxation, and suggesting mobilization of distinct mechanisms underlying muscle relaxation.

Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder

“…Several authors have shown that adenosine directly relaxes pre-contracted urinary bladder detrusor strips in different species [10][11][12][13][14], including humans [15]. However, our results clearly indicate that adenosine-induced relaxation of detrusor contractions requires high (unphysiological) millimolar concentrations of the nucleoside.…”

“…Despite the observation that adenosine is able to relax precontracted detrusor strips from the human bladder [15], we found that this is only valid for concentrations of the nucleoside in the millimolar range (Fig. 4).…”

“…Previous studies have shown that adenosine partially relaxes pre-contracted urinary bladder detrusor strips exposed to carbachol, acetylcholine (ACh), or potassium depolarization in rats, guinea-pigs [10][11][12][13][14], and humans [15]. Besides direct actions of adenosine on P1 receptors located on detrusor smooth muscle fibers, the nucleoside and its analogues may act indirectly by inhibiting nerve-evoked contractions as demonstrated in rats [10,13,14,16], guinea pigs [14], cats [17], and humans [18].…”

Inhibition of cholinergic neurotransmission by β3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders

“…Adenosine directly relaxes precontracted urinary bladder detrusor strips in different species (1,8,9,33,43), including humans (51). Notwithstanding this, we recently showed that adenosine-induced relaxation of detrusor contractions requires high (millimolar) concentrations of the nucleoside compared with those required to decrease nerve-evoked ACh release from human detrusor strips (54).…”

Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI‐RS 2017

“…Adenosine is a breakdown product of ATP via endonucleotidases, and stimulates different types of the P1 class of adenosine receptors (A 1 , A 2A , A 2B , and A 3 ). In the human bladder, adenosine relaxes contractions induced by agonists, and electrical stimulation of nerves . and reduces stretch‐activated urothelial ATP release .…”