Phosphodiesterase-5 inhibition: the molecular biology of erectile function and dysfunction

This article discusses the role of phosphodiesterase-5 (PDE-5) inhibition in the molecular biology of erectile function and dysfunction. Commercially marketed PDE-5 inhibitors are highly specific for PDE-5, and in the face of continuing cyclic GMP (cGMP) synthesis,elevate cellular cGMP. This elevation results from direct competitive inhibition of PDE-5 and from blocking the negative feedback regulation of the enzyme. Elevation of cGMP activates cGMP-dependent protein kinase, which mediates the effects of the cGMP-signaling pathway to decrease smooth muscle tone and dilate penile vascular smooth muscle. By exploiting features of PDE-5 regulatory mechanisms that modulate PDE-5 function, the inhibitors enhance their own potencies.