RhoA/Rho-kinase in erectile tissue : mechanisms of disease and therapeutic insights

• Published in: Clinical science (1979) Vol. 110; no. 2; pp. 153 - 165
• Main Authors: JIN, Liming, BURNETT, Arthur L
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.02.2006
• Subjects: Biological and medical sciences; Erectile Dysfunction - drug therapy; Erectile Dysfunction - enzymology; Female; General aspects; Humans; Intracellular Signaling Peptides and Proteins; Male; Medical sciences; Protein-Serine-Threonine Kinases - metabolism; rho-Associated Kinases; rhoA GTP-Binding Protein - metabolism; Sexual Dysfunction, Physiological - enzymology; Signal Transduction - physiology; Erection disorders; Disease; Rho-kinase; Smooth muscle; Corpus cavernosum; Knowledge; Mechanism; RhoA; erectile dysfunction; Medicine; Tissue; Treatment; Penis; Male genital diseases
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS20050255

Penile erection is a complicated event involving the regulation of corpus cavernosal smooth muscle tone. Recently, the small monomeric G-protein RhoA and its downstream effector Rho-kinase have been proposed to be important players for mediating vasoconstriction in the penis. RhoA/Rho-kinase increases MLC (myosin light chain) phosphorylation through inhibition of MLCP (MLC phosphatase) thereby increasing Ca2+ sensitivity. This review will outline the RhoA/Rho-kinase signalling pathway, including the upstream regulators, guanine nucleotide exchange factors, GDP dissociation inhibitors and GTPase-activating proteins. We also summarize the current knowledge about the physiological roles of RhoA/Rho-kinase in both male and female erectile tissues and its aberrations contributing to erectile dysfunction in several disease states. Understanding the RhoA/Rho-kinase signalling pathway in the regulation of erection is important for the development of therapeutic interventions for erectile dysfunction.