Resveratrol Activates Membrane‐bound Guanylate Cyclase in PC12 Cells

Resveratrol, found in wine and grapes, has cardioprotective and anticarcinogenic properties. The guanylate cyclase-cyclic GMP (cGMP) system is known to mediate the effects of vasoactive hormone and ligands such as atrial natriuretic factor and nitric oxide. It is possible that resveratrol exerts its effects by activating guanylate cyclase. This study was conducted to examine whether resveratrol can affect the guanylate cyclase-cGMP system in PC12 cells. The results showed that resveratrol dose-dependently increased cGMP levels. It inhibited membrane-bound guanylate cyclase activity stimulated by atrial natriuretic factor, but had no effect on soluble guanylate cyclase activity stimulated by sodium nitroprusside. It also directly stimulated membrane-bound guanylate cyclase activity in PC12 cell membranes. These results show that resveratrol increases cGMP formation by activating membrane-bound, but not soluble, guanylate cyclase.