Effects of simple aromatic compounds and flavonoids on Ca2+ fluxes in rat pituitary GH(4)C(1) cells

The biological activity of phenolic compounds from plants is well documente d in vitro, but little is known about the possible effect of simple aromati c compounds and flavonoids on voltage-operated Ca2+ channels (VOCCs). In pi tuitary cells, several intracellular pathways may regulate the activity of VOCCs. In this study, we investigated the effect of nine phenylpropanes and metanes, and 20 flavonoids on high K+-induced Ca-45(2+) entry in clonal ra t pituitary GH(4)C(1) cells. At the highest dose tested (20 mug/ml), flavon e (a flavone) inhibited Ca-45(2+) entry by 63.5%, naringenin (a flavanone) by 56.3% and genistein tan isoflavone) by 54.6%. The phenylmetane derivativ e octyl gallate was the most potent compound tested, with an IC50 value of 15.0 mug/ml. The IC50 value for the reference compound verapamil hydrochlor ide was 3.0 mug/ml. In sharp contrast to the above, the flavonols quercetin and morin potentiated Ca-45(2+) entry. At 70 mug/ml. quercetin increased C a-45(2+) entry by 54.1% and morin by 48.0%. Quercetin increased the cellula r cAMP content in a concentration-dependent manner. H 89. an inhibitor of p rotein kinase A, inhibited the effect of quercetin on Ca-45(2+) entry. The results thus suggest that the effect of quercetin is the result of a protei n kinase A-mediated activation of VOCCs. Quercetin induced a rapid and mark ed increase in both the transient (143.1 +/- 4.2%) and delayed (198.8 +/- 1 0.0%) Ca2+ currents, measured by the whole cell patch clamp technique. The onset of the inhibitory effect of octyl gallate was slow, but resulted in a n almost complete inhibition of both Ca2+ currents. (C) 2001 Elsevier Scien ce B.V. All rights reserved.