Phosphodiesterase-5 inhibition: the molecular biology of erectile function and dysfunction |
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Authors: | Francis Sharron H Corbin Jackie D |
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Institution: | Department of Molecular Physiology and Biophysics, Light Hall, Room 702, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA. sharron.francis@vanderbilt.edu |
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Abstract: | 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. |
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