Abstract: The role of extracellular nucleotides and apyrase enzymes in the guard cells that border stomata in regulating stomatal aperture and the plant's resistance to drought and pathogens is disclosed herein. Expression of apyrases APY1 and APY2, in guard cell protoplasts is strongly correlated with cell growth, cell secretory activity and with conditions that favor stomatal opening. Both short-term inhibition of ectoapyrase activity and long-term suppression of APY1 and APY2 transcript levels significantly disrupt normal stomatal behavior in light. Furthermore, two punnoceptor inhibitors in mammals, pyridoxalphosphate-6-azo-phenyl-2?,4?-disulphonic acid (PPADS) and Reactive Blue 2, block ATPS- and ADP?S-induced opening and closing, and also partially block the ability of abscisic acid (ABA) to induce stomatal closure, and light-induced stomatal opening.