In some cells a supersensitive adenylyl cyclase response follows hormonal inhibition of the enzyme. We have compared the effect of pre-treatment with noradrenaline in RINm5F cells to that in cells known to demonstrate supersensitivity. In NG108-15 cells, 12 or 24 hours pre-treatment with 1-10 microM noradrenaline markedly enhanced forskolin (1 microM) stimulated cAMP accumulation compared to that in untreated cells (12 h, 429 +/- 123 vs 72 +/- 8 pmol/mg protein; 24 h 190 +/- 32 vs 82 +/- 10 for treated and untreated cells, respectively). In a second cell, HT29-18, 30 min pre-treatment with 10 microM noradrenaline enhanced forskolin (10 microM) stimulated cAMP accumulation from 47 +/- 13 pmol/mg protein to 405 +/- 109 pmol/mg protein. In contrast, pre-treatment of RINm5F cells with noradrenaline under the same conditions did not enhance the forskolin response. These data indicate that noradrenaline which induces a supersensitive adenylyl cyclase response in NG108-15 and HT29-18 cells does not induce the response in the insulin secreting cell RINm5F.