CHANGES IN ADENOSINE A(1)-RECEPTOR AND A(2)-RECEPTOR EXPRESSION DURING ADIPOSE CELL-DIFFERENTIATION

Two adenosine receptors A(1) and A(2) are associated with either stimu lation (A(2)) or inhibition (A(1)) of adenylate cyclase. Using the clo nal cell line Ob1771, we have studied the expression of the two recept ors during the process of adipose conversion accelerated by exposure t o dexamethasone and 3-isobutyl-1-methylxanthine (IBMX) during the firs t 3 days post-confluence. The effects mediated by the two receptors on preadipocyte differentiation and adipocyte metabolism were also inves tigated. The two adenosine agonists NECA and PIA were used as preferen tial agonists of the A(2)- and A(1)-receptor, respectively. In preadip ose cells (just confluent), both of the mouse clonal line and human pr imary 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 f orskolin-stimulated cAMP production i.e., NECA was dearly inhibitory i n the femto- to picomolar concentration range whereas this effect grad ually diminished at higher concentrations. The effect of PIA in 16-day post-confluent adipose cells however, was purely inhibitory on both c AMP production (IC50: 33.52 +/- 0.44 fM) and lipolysis (64% +/- 7%; P < 0.01). These findings were corroborated by Northern blot analysis wh ich revealed A(1)-receptor mRNA to be exclusively expressed in the mat ure adipocytes, whereas A(2)-receptor mRNA gradually declined during t he differentiation process except in 16-day post-confluent cells. In a ddition, NECA significantly enhanced the effect of corticosterone-indu ced differentiation by 46.8% (P < 0.05) but failed to have any adipoge nic potency acting either alone or in concert with carbaprostacyclin ( cPGI(2)). Thus, endogenous adenosine may have a bimodal action on adip ose tissue metabolism mediated through stimulatory A(2)- and inhibitor y A(1)-receptors, respectively, as a function of adipose conversion.