Microdialysis of intercellular adenosine concentration in subcutaneous tissue in humans

To determine the intercellular adenosine concentration the periumbilical subcutaneous interstitial fluid was investigated in five healthy subjects with two single dialysis fiber catheters perfused with isotonic saline at a rate of 2.5 mul/min. A newly developed in situ calibration technique (29) allows an estimation of the adenosine concentration in the perfusate equilibrating with the surrounding medium, i.e., the concentration in the interstitial fluid. The mean interstitial adenosine concentration was 128 +/- 26 nM (range 25-300 nM). The effect of these adenosine concentrations on adipose tissue metabolism was investigated in isolated human fat cells. The influence of 5 and 10 nM 2-chloroadenosine, which is equipotent to 150 and 300 nM adenosine, on the dose-response curve for the lipolytic effect of norepinephrine and the stimulatory effect of insulin on glucose transport was studied. 2-Chloroadenosine at 10 nM decreased basal lipolysis 53 +/- 8% and shifted the dose-response curve for norepinephrine approximately twofold to the right. At 5 nM, 2-chloroadenosine only slightly shifted the dose-response curve, whereas basal lipolysis was not significantly reduced. 2-Chloroadenosine at either concentration had no significant effect on basal or insulin-stimulated glucose transport. In conclusion, endogenous adenosine can reach concentrations in human subcutaneous tissue sufficient for an important modulating effect on lipolysis in vivo.