RT Journal Article SR Electronic T1 Blockade by nanomolar resveratrol of quantal catecholamine release in chromaffin cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP mol.110.066423 DO 10.1124/mol.110.066423 A1 Jose Carlos Fernandez-Morales A1 Matilde Yanez A1 Francisco Orallo A1 Lorena Cortes A1 Jose Carlos Gonzalez A1 Jesus-Miguel Hernandez-Guijo A1 Antonio G. Garcia A1 Antonio Miguel G. de Diego YR 2010 UL http://molpharm.aspetjournals.org/content/early/2010/07/14/mol.110.066423.abstract AB The cardiovascular protecting effects of resveratrol, an antioxidant polyphenol present in grapes and wine, have been attributed to its vasorelaxing effects as well as to its anti-inflammatory, antioxidant, and antiplatelet actions. Inhibition of adrenal catecholamine release has also been recently implicated in its cardio-protecting effects. Here, we have studied the effects of nanomolar concentrations of resveratrol on quantal single-vesicle catecholamine release in isolated bovine adrenal chromaffin cells. We have found that 30-300 nM concentrations of resveratrol blocked the acetylcholine (ACh) and high K+-evoked quantal catecholamine release, amperometrically measured with a carbon fibre microelectrode. At these concentrations, resveratrol did not affect the whole-cell inward currents through nicotinic receptors or voltage-dependent sodium and calcium channels, neither the ACh- or K+-elicited transients of cytosolic Ca2+. Blockade by nanomolar resveratrol of secretion in ionomycin- or digitonin-treated cells suggests an intracellular site of action beyond Ca2+-dependent exocytotic steps. The fact that nanomolar resveratrol augmented cGMP is consistent with the view that resveratrol could be blocking the quantal secretion of catecholamine through a nitric oxide linked mechanism. Because this effect occurs at nanomolar concentrations, our data are relevant in the context of the low circulating levels of resveratrol found in moderate consumers of red wines, that could afford cardioprotection by mitigating the catecholamine surge occurring during stress.