The effect of a cAMP analogue on Ca2+ ionophore-, antigen- and agonist-induced inositol phosphate release in rat basophilic leukaemia (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-IP 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 GTP gamma S-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.
Galadari
S H
SH
Imperial College of Science, Technology and Medicine, London, U.K.
Morris
H R
HR
Di Marzo
V
V
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000941:Antigens / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000276:immunology / Q000378:metabolism*; D015471:Leukemia, Basophilic, Acute / Q000276:immunology / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
D000941:Antigens; D007295:Inositol Phosphates; D016859:Lipoxygenase Inhibitors; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D014665:Vasodilator Agents; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019830:Adenosine-5'-(N-ethylcarboxamide); D000001:Calcimycin; D000241:Adenosine