ADENOSINE STIMULATES 5'-NUCLEOTIDASE ACTIVITY IN RAT MESANGIAL CELLS VIA A2-RECEPTORS

Because A2 adenosine receptor activation stimulates adenylate cyclase and cyclic AMP induces 5'-nucleotidase expression in rat mesangial cel ls, we examined the effect of adenosine and its analogs on 5'-nucleoti dase activity in these cells. A2 adenosine receptors were characterize d using [H-3]5'-N-ethylcarboxamidoadenosine (NECA) as a tracer. There was a single group of receptor sites with a K(D) value of 0.53 muM and a number of sites of 1,317 fmol/mg. [H-3]NECA binding was inhibited p referentially by A2 adenosine analogs and antagonists. Similarly, the order of potency for cAMP stimulation was in favour of A2 adenosine an alogs. Rat mesangial cells expressed surface 5'-nucleotidase activity. Exposure of cells for 48 h to adenosine analogs showed that at low co ncentrations A2 analogs stimulated 5'-nucleotidase activity. These res ults indicate that adenosine upregulates activity of 5'-nucleotidase, the enzyme responsible for its local formation, via A2 receptor stimul ation and increase in cAMP production.