Meeting Abstract

31.4  Thursday, Jan. 5  The flavone, chrysin, relaxes cholecystokini or KCl-induced tension in male guinea pig gallbladder strips through multiple signaling pathways KLINE, L.W.*; KARPINSKI, E.; University of Alberta, Edmonton; University of Alberta, Edmonton lkline@ualberta.ca

The flavonoids are a large group of plant-derived pholic compounds with biological effects. Chrysin has relaxant effects on both vascular and intestinal smooth muscle. In this laboratory an in vitro technique was used to determine the effects of chrysin on male guinea pig gallbladder strips, and to determine which second messenger system(s) mediated the chrysin-induced relaxation. Chrysin relaxed cholecystokinin octapeptide (CCK) or KCl-induced tension in a concentration dependent manner. When chrysin was added to the chambers 3 min prior to the KCl, a significant decrease in tension was observed (1.12+/-0.12 vs. 0.64+/-0.08g). To determine if the PKA/cAMP second messenger system mediated the chrysin-induced relaxation of CCK-induced tension, PKA-IM 14-22 amide myristolated (PKA-IM) was used. PKA-IM caused a significant decrease in chrysin-induced relaxation (69.8+/-3.5 vs. 56.4+/-2.8%). Neither the PKG inhibitor, KT5823,the NO synthase inhibitor, L-NMMA, nor the protein tyrosine kinase inhibitor, genistein,had a significant effect on the amount of chrysin-induced relaxation. When the PKC inhibitors, bisindolymaleimide IV and chelerythrine Cl- were used together, a significant reduction in chrysin-induced relaxation (57.9+/-4.4 vs. 52.2+/-5.1%) was observed. 2-APB, an inhibitor of IP3 induced Ca2+ release, significantly decreased the amount of chrysin-induced relaxation (60.7+/-6.0 vs. 49.1+/-2.5%). The results show that the chrysin-induced relaxation is mediated by the PKA/cAMP and PKC second messenger systems. The blocking of extracellular Ca2+ entry and blocking intracellular Ca2+ release are also involved in mediating the chrysin effect.