Differential effect of flavonoids on inhibition of secretion and accumulation of secretory granules in rat basophilic leukemia cells.
Rat basophilic leukemia (RBL) cells resemble mucosal mast cells (MMC) and develop few secretory granules under normal culture conditions. RBL cells have been used for the study of secretion and for the possible involvement of MMC in food allergies and irritable bowel syndrome (IBS). The flavonoid quercetin is one of very few molecules that inhibit RBL cell proliferation and constitutive histamine release; it also induces synthesis of rat mast cell protease (RMCP) II and accumulation of secretory granules. Even though quercetin is available as a food supplement over the counter, some early studies had indicated it may be carcinogenic. We, therefore, compared the effect of quercetin to that of other flavonoids with similar structure. Flavone, kaempferol, myricetin and morin were investigated for their action on RBL cell secretion of beta-hexosaminidase stimulated by anti-DNP serum and DNP-BSA, as well as on secretory granule development. Quercetin, myricetin and kaempferol inhibited RBL cell secretion significantly only at 10(-4) M. Flavone inhibited secretion at 10(-4), 10(-5) and 10(-6) M; it also maximally induced secretory granule accumulation as evidenced by light and electron microscopy. In contrast, morin which differs structurally only by one extra hydroxyl group had minimal effect. These results indicate that flavone is capable of inhibiting stimulated secretion and inducing secretory granule development at reasonable concentrations.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
M
M
Alexandrakis
L
L
Singh
W
W
Boucher
R
R
Letourneau
P
P
Theofilopoulos
T C
TC
Theoharides
D000818:Animals; D003594:Cytoplasmic Granules / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000648:ultrastructure; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D005419:Flavonoids; D011794:Quercetin; D001619:beta-N-Acetylhexosaminidases