Changes in adenosine A1- and A2-receptor expression during adipose cell differentiation.

Two adenosine receptors A1 and A2 are associated with either stimulation (A2) or inhibition (A1) of adenylate cyclase. Using the clonal cell line Ob1771, we have studied the expression of the two receptors during the process of adipose conversion accelerated by exposure to dexamethasone and 3-isobutyl-l-methylxanthine (IBMX) during the first 3 days post-confluence. The effects mediated by the two receptors on preadipocyte differentiation and adipocyte metabolism were also investigated. The two adenosine agonists NECA and PIA were used as preferential agonists of the A2- and A1-receptor, respectively. In preadipose cells (just confluent), both of the mouse clonal line and human primary culture, NECA dose-dependently stimulated cAMP production with a significant higher potency (P < 0.01) than did PIA. In adipose cells (16-day post-confluent) NECA was found to exert a biphasic effect on forskolin-stimulated cAMP production: i.e., NECA was clearly inhibitory in the femto- to picomolar concentration range whereas this effect gradually diminished at higher concentrations. The effect of PIA in 16-day post-confluent adipose cells however, was purely inhibitory on both cAMP production (IC50: 33.52 +/- 0.44 fM) and lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern blot analysis which revealed A1-receptor mRNA to be exclusively expressed in the mature adipocytes, whereas A2-receptor mRNA gradually declined during the differentiation process except in 16-day post-confluent cells. In addition, NECA significantly enhanced the effect of corticosterone-induced differentiation by 46.8% (P < 0.05) but failed to have any adipogenic potency acting either alone or in concert with carbaprostacyclin (cPGI2). Thus, endogenous adenosine may have a bimodal action on adipose tissue metabolism mediated through stimulatory A2- and inhibitory A1-receptors, respectively, as a function of adipose conversion.