The regulation of Protein kinase A signaling pathway is controlled by the cellular cAMP level. The level of cAMP in the cell is regulated by the enzymes adenylate cyclase, which synthesizes the cAMP from ATP, and cAMP phosphodiesterase, which degrades the cAMP to AMP. The PDE1 and PDE2 genes encode two phosphodiesterases with low and high affinity for cAMP, respectively. The NTH1 gene encodes the neutral trehalase enzyme, which is responsible for stress-accumulated trehalose degradation, and its expression is regulated by PKA. The aim of this study was to examine the effect of PDE1 and PDE2 gene products on the expression of the NTH1 gene and reserve carbohydrate metabolism in both stressful and restoring conditions. Thus, the expression of the NTH1 was assessed under nitrogen starvation, heat stress, and recovery period by inserting the plasmid containing the Nth1-LacZ gene fusion into pde1∆, pde1∆, and wild-type yeast strains. The expression of the NTH1 gene was shown to be lower than that of the wild-type under normal conditions, heat stress, nitrogen starvation, and also during the replenishment period in pde1∆ and pde1∆ yeast cells. The accumulation of trehalose and glycogen was shown to be dramatically enhanced in pde1∆ yeast cells. However, deletion of the PDE2 gene did not lead to a significant change in trehalose and glycogen accumulation comparable to that found in the wild-type. These results indicate that the PDE1 gene product, rather than PDE2, is required for the downregulation of reserve carbohydrate metabolism. Consequently, the Pde1 protein is considered to exert yet-unidentified regulatory control over the Pde2 protein.