Down-regulation of adenosine A(2A) receptors upon NGF-induced differentiation of PC12 cells

PC12 cell differentiation was induced by one week of nerve growth factor (NGF) treatment and adenosine A(2A) receptor expression and activity were analysed. Undifferentiated PC12 cells expressed very high levels of adenosine A(2A) receptors (congruent to 2 pmol/mg) and exhibited strong cyclic AMP (cAMP) responses when stimulated with the selective adenosine A(2A) receptor agonist 2-[p-(2-carbonylethyl) phenylethylamino-5'-N-ethylcarboxamidoadenosine]. NGF-induced differentiation was accompanied by a down-regulation of adenosine A(2A) receptors: receptor binding decreased to 500 fmol/mg, immunoreactive A(2A) receptor protein was decreased by about half and cAMP production was reduced by 60%. In situ hybridization experiments demonstrated a heterogenous distribution of A(2A) receptor mRNA and a decreased number of strongly labelled cells after NGF treatment. Stimulation of the cells with the non-selective adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA) inhibited NGF-induced mitogen-activated protein kinase activation. These results thus show that NGF-induced differentiation of PC12 cells is accompanied by a decrease in A(2A) receptor-mediated cAMP accumulation. This might be a way for PC12 cells to counteract an inhibitory effect of A(2A) receptor activation on some aspects of neurotrophin signalling. (C) 1997 Elsevier Science Ltd.