Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine.

Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 mumol/l DL-isoproterenol was inhibited markedly less by N6-(phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P less than 0.01). Glucose uptake was more responsive to N6-(phenylisopropyl)adenosine in adipocytes from control than treated animals (P less than 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 +/- 279 and 1988 +/- 575 fmol/mg protein; mean +/- SEM). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) alpha subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6-(phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment.