Phenotypical effect of phosphodiesterase 5 (PDE5) inhibitor on behavioral activities of fruit fly Drosophila melanogaster

Abstract

Phosphodiesterase 5 (PDE5) inhibitor is a class of drugs currently used to treat erectile dysfunction. Physiologically, inhibition of PDE5 may lead to vasodilation, blood flow increment, and penile erection. However, PDE5 inhibitors have been reported not only to modify the function of the male reproductive organ but also to influence other physiological systems. To explore the effect of PDE5 inhibitor on metazoan physiological systems, a fruit fly (Drosophila melanogaster) model organism is used since the catalytic domain of fruit fly PDE5/6 shares a high similarity of amino acid sequence (58%) with the PDE5 of humans. This study aimed to investigate whether the effect of PDE5 inhibition by sildenafil is phenotypically observable as changes in the behavioral states. Two behavioral phenotypes of D. melanogaster, negative geotaxis, and ethanol sensitivity, were used as test parameters in this explorative study. The results demonstrated that sildenafil had a significant effect on reducing locomotor activity, as reflected by negative geotaxis assay, but it had no influence on the fruit fly sensitivity to ethanol. Taken together, our results suggested that PDE5 inhibition might impair the physiological condition of the metazoan species. Also, an explorative study using D. melanogaster might offer valuable insight as a model organism in the discovery and repurposing approach of PDE5 inhibitor.