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Volume 4, Issue 3, Pages (June 2006)

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Presentation on theme: "Volume 4, Issue 3, Pages (June 2006)"— Presentation transcript:

1 Volume 4, Issue 3, Pages 96-108 (June 2006)
Physiology of Erectile Function: An Update on Intracellular Molecular Processes  Annamaria Morelli, Sandra Filippi, Linda Vignozzi, Rosa Mancina, Mario Maggi  EAU-EBU Update Series  Volume 4, Issue 3, Pages (June 2006) DOI: /j.eeus Copyright © 2006 European Association of Urology Terms and Conditions

2 Fig. 1 Schematic representation of neurophysiological control of erection. NO, nitric oxide; T11-L2, thoraco-lumbar tract of the spinal cord; S2-S4, sacral tract of the spinal cord. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

3 Fig. 2 Summary of the contraction/relaxation mediating transmitters in the penis. NPY, neuropeptide Y; PGF2α, prostanoid F2α; TXA2, tromboxane A2; VIP, vasointestinal peptide; PGE1 and PGE2, prostaglandin E1 and E2. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

4 Fig. 3 Intracellular signalling leading to smooth muscle cell contraction in corpora cavernosa and determining the flaccid state of the penis. NA, noradrenaline; ET-1, endothelin-1; PLC, phospholipase C; PIP, phosphatidylinositol biphosphate; IP3, inositol-3-phosphate; DAG, diacylglycerol; PKC, protein kinase C; CaM, calmodulin; MLC, myosin light chain; MLCK, MLC kinase; SR, sarcoplasmic reticulum. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

5 Fig. 4 Intracellular molecular mechanism of smooth muscle cell contraction via RhoA/ROK mediated calcium-sensitizing pathway. NA, noradrenaline; ET-1, endothelin-1; GPCR, G protein coupled receptor; PLC, phospholipase C; GTP, guanosine triphosphate; GDP, guanosine diphosphate; GEF, guanine nucleotide exchange factor; GAP, GTPase-activating protein; GDI, GDP dissociation inhibitor; MLC, myosin light chain; MLCK, MLC kinase; MLCP, MLC phosphatase; ATP, adenosine triphosphate; SR, sarcoplasmic reticulum. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

6 Fig. 5 cGMP-mediated intracellular signalling leading to smooth muscle cell relaxation in corpora cavernosa and determining the erection state of the penis. NANC, nonadrenergic noncholinergic; NO, nitric oxide; sGC, soluble guanylate cyclase; GTP, guanosine triphosphate; GMP, guanosine monophosphate; cGMP, cyclic GMP; PKG, cGMP-dependent protein kinase; PDE5, phosphodiesterase type 5; MLC, myosin light chain; MLCK, MLC kinase; MLCP, MLC phosphatase; SR, sarcoplasmic reticulum. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

7 Fig. 6 Inhibition curves of cGMP-hydrolysing activity induced by PDE5 inhibitors (vardenafil, sildenafil, tadalafil) in corpora cavernosa extracts from human penile biopsies. Aliquots of tissue homogenates (0.1mg protein/ml) were incubated with 0.5μM cGMP and 0.1μM [3H]cGMP in absence or in presence of vardenfil (10−13–10−6M), sildenafil (10−11–10−6M) and tadalafil (10−11–10−6M). Ordinate: cGMP hydrolysing activity expressed as conversion percentage; Conversion (%)=[products count/(substrate+products counts)]×100. Abscissa: inhibitor concentration. Inhibition curves obtained in three different experiments were fitted simultaneously with the program ALLFIT using the four-parameter logistic equation. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions

8 Fig. 7 Mechanisms of action of testosterone on erectile function. By maintaining the correct balance between NOS and PDE5 expression/activity, T regulates intracellular cGMP levels in penile tissue and thereby smooth muscle relaxation for erectile function. On the other hand, T exerts a trophic and differentiating action for cavernous smooth muscle cells to maintain integrity of erectile structures. NOS, nitric oxide synthase; PDE5, phosphodiesterase type 5. EAU-EBU Update Series 2006 4, DOI: ( /j.eeus ) Copyright © 2006 European Association of Urology Terms and Conditions


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