The effect of a cAMP analogue on Ca²⁺ ionophore-, antigen- and agonist-induced inositol phosphate release in rat basophilic leukemia (RBL-1) cells

The effect of the stable cAMP analogue 8-Br-cAMP on leukotriene D₄ (LTD₄)-, 5′-N-ethyl-carboxamidoadenosine (NECA)-, antigen- and Ca²⁺ ionophore-induced inositol phosphate (IP) production was studied in RBL-1 cells. The cAMP analogue significantly inhibited LTD₄- and antigen induced-1P production, thus supporting the hypothesis of a negative interaction between cAMP and phosphoinositide breakdown in blood cells. Ionophore-induced IP release, which was blocked by a 5-lipoxygenase inhibitor and by a LT-receptor antagonist, and therefore is probably mediated by LTs, was also inhibited by 8-Br-cAMP. NECA-induced IP release was not significantly inhibited by the cyclic nucleotide, thus showing that the effect described herein is not a general action on receptor-activated phospholipase C. 8-Br-cAMP did, however, inhibit GTPγS-induced IP release in permeabilised RBL-1 cells, thus suggesting that the inhibition does not occur at the receptor level but might be due, at least in part, to an effect on some receptor-coupled G proteins.