Sodium saccharin inhibits adenylyl cyclase activity in non-taste cells.

We have studied the in vitro effect of sodium saccharin (NaSacch) on the rat adipocyte adenylyl cyclase complex. NaSacch (2.5-50 mM) inhibited significantly in a dose-dependent manner basal and isoproterenol-stimulated cAMP accumulation on isolated rat adipocytes. Similarly, NaSacch (2.5-50 mM) inhibited forskorin-stimulated adenylyl cyclase activity measured in the presence of Mg2+-ATP on adipocyte, astrocyte and thyrocyte membrane fractions. In contrast, NaSacch did not inhibit but slightly increased the forskolin-stimulated adenylyl cyclase activity measured in the presence of Mn2+-ATP and GDP beta S, a stable GDP analogue. The effect of NaSacch was not mediated through either the A(1)-adenosine receptor (A(1)R) or the alpha(2)-adrenergic receptor (alpha(2)AR). The inhibitory effect of NaSacch was additive to that of A(1)R agonist and was not blocked by the addition of the alpha(2)AR antagonist RX 821002. Pretreatment of adipocytes with pertussis toxin slightly attenuated but did not abolish the inhibitory effect of NaSacch on forskolin-stimulated adenylyl cyclase activity on membrane fractions. These data suggest that the inhibitory effect of NaSacch on forskolin stimulated-adenylyl cyclase in adipocytes does not imply only Gi protein but also other direct or indirect inhibitory pathway(s) which remain to be determined. (C) 1997 Elsevier Science Inc.