Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: On the role of secreted adenosine deaminase

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

“…Therefore, the evoked [ 3 H]ACh release was calculated by subtracting the basal tritium outflow from the total tritium outflow during the stimulation period (see, e.g., [21][22][23]). Likewise, stimulation-evoked release of ATP was calculated by subtracting the basal release, measured in the sample collected before stimulation, from the total release of the nucleotide determined after stimulus application [23][24][25].…”

“…After equilibrium, the preparations were incubated with 30 μM of ATP or AMP (zero time). Samples of 75 μL were collected from the organ bath at different times up to 45 min for HPLC (with UV detection) analysis (LaChrome Elite; Merck, Germany) of the variation of substrate disappearance and product formation [21,22,26]. The stoichiometry of ATP and AMP conversion into their metabolites was kept unaltered (30 μM).…”

Purinergic receptors and synaptic transmission in enteric neurons

“…Adenosine may then act at its own receptors before itself being broken down to inosine by the enzyme adenosine deaminase. Studies in the ENS have failed to show an appreciable effect when ATP is applied and P1 receptors are blocked [35,36] or when breakdown of ATP is prevented [37], suggesting that this route for adenosine formation, although plausible, may not be physiologically relevant.…”

“…Electrically evoked adenosine release has been demonstrated from myenteric plexuslongitudinal muscle preparations [38]. Myenteric neurons were the main source of endogenous adenosine, since blockade of action potentials with tetrodotoxin (1 μM) or omission of Ca 2+ (plus EGTA, 1 mM) in the solution essentially abolished nucleoside release, while adenosine outflow remained unchanged when smooth muscle contractions were prevented by nifedipine [37]. Adenosine can be released under basal conditions, but its release is often increased under metabolically stressful conditions such as ischemia, inflammation, or cell damage [e.g., 39].…”

Peripheral Nervous System

“…Endogenous adenosine, some of which arises from extracellular ATP metabolism, probably acting through presynaptic A 1 receptors, inhibits SP release from perfused networks of myenteric ganglia from guinea pig ileum and is postulated to be an important contributor to the overall inhibitory tone present in myenteric ganglia networks (Broad et al 1993;Moneta et al 1997). Subsequent studies have shown differential gene expression of A 1 , A 2A , A 2B and A 3 receptors in human enteric neurons , and fine-tuning modulation of myenteric and submucosal motoneuron activity by endogenous adenosine has been claimed acting largely via presynaptic A 1 receptors Correia-de-Sá et al 2006). A neuroprotective role for adenosine in ischaemia has been postulated, consistent with a demonstrated relationship between interstitial adenosine in the myenteric neural network and prevailing O 2 tension (Deshpande et al 1999).…”