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Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract.

Abstract

The clinical data on the use of the orally active phosphodiesterase (PDE) type 5 inhibitors sildenafil (VIAGRA™), vardenafil (LEVITRA™), and tadalafil (CIALIS™) for the treatment of male erectile dysfunction have boosted research activities on the physiology and pharmacology of the organs of the lower urinary tract (LUT). This includes both intracellular signal transduction in the prostate, urinary bladder (detrusor), and urethra, as well as central brain and spinal cord pathways controlling the function of the LUT. Such efforts provided the basis for the development of new therapeutic modalities into the management of dysfunctions/ syndromes of the LUT, some of which are already offered to the patients. The pharmacological treatment of the overactive bladder and the so-called benign prostatic syndrome, including LUT symptomatology and bladder outlet obstruction secondary to benign prostatic enlargement, has primarily focused on selective, orally available drugs acting by influencing intracellular regulatory mechanisms. These agents are regarded efficacious, have a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. Better understanding of the functional significance of proteins related to cyclic nucleotide-dependent pathways, such as nitric oxide synthase, cytosolic and membrane-bound guanylyl cyclases, PDE isoenzymes and cyclic AMP- and cyclic GMP-binding protein kinases, the relative distribution in tissues of the LUT, and the consequences for urogenital function, seems to be of particular interest in order to identify new or more selective pharmacological approaches to manage disorders of the LUT. The present review focuses on cyclic nucleotide-related targets involved in the control of the function of the bladder, prostate, and urethra and the significance of those proteins in the process of evolving new pharmacological options for the treatment of LUT symptoms secondary to benign prostatic hyperplasia as well as dysfunctions of the storage and voiding capability of the urinary bladder.

Authors+Show Affiliations

Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany. sue_de_99@yahoo.deNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21290241

Citation

Uckert, Stefan, and Markus A. Kuczyk. "Cyclic Nucleotide Metabolism Including Nitric Oxide and Phosphodiesterase-related Targets in the Lower Urinary Tract." Handbook of Experimental Pharmacology, 2011, pp. 527-42.
Uckert S, Kuczyk MA. Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. Handb Exp Pharmacol. 2011.
Uckert, S., & Kuczyk, M. A. (2011). Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. Handbook of Experimental Pharmacology, (202), 527-42. https://doi.org/10.1007/978-3-642-16499-6_23
Uckert S, Kuczyk MA. Cyclic Nucleotide Metabolism Including Nitric Oxide and Phosphodiesterase-related Targets in the Lower Urinary Tract. Handb Exp Pharmacol. 2011;(202)527-42. PubMed PMID: 21290241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclic nucleotide metabolism including nitric oxide and phosphodiesterase-related targets in the lower urinary tract. AU - Uckert,Stefan, AU - Kuczyk,Markus A, PY - 2011/2/4/entrez PY - 2011/2/4/pubmed PY - 2011/5/13/medline SP - 527 EP - 42 JF - Handbook of experimental pharmacology JO - Handb Exp Pharmacol IS - 202 N2 - The clinical data on the use of the orally active phosphodiesterase (PDE) type 5 inhibitors sildenafil (VIAGRA™), vardenafil (LEVITRA™), and tadalafil (CIALIS™) for the treatment of male erectile dysfunction have boosted research activities on the physiology and pharmacology of the organs of the lower urinary tract (LUT). This includes both intracellular signal transduction in the prostate, urinary bladder (detrusor), and urethra, as well as central brain and spinal cord pathways controlling the function of the LUT. Such efforts provided the basis for the development of new therapeutic modalities into the management of dysfunctions/ syndromes of the LUT, some of which are already offered to the patients. The pharmacological treatment of the overactive bladder and the so-called benign prostatic syndrome, including LUT symptomatology and bladder outlet obstruction secondary to benign prostatic enlargement, has primarily focused on selective, orally available drugs acting by influencing intracellular regulatory mechanisms. These agents are regarded efficacious, have a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. Better understanding of the functional significance of proteins related to cyclic nucleotide-dependent pathways, such as nitric oxide synthase, cytosolic and membrane-bound guanylyl cyclases, PDE isoenzymes and cyclic AMP- and cyclic GMP-binding protein kinases, the relative distribution in tissues of the LUT, and the consequences for urogenital function, seems to be of particular interest in order to identify new or more selective pharmacological approaches to manage disorders of the LUT. The present review focuses on cyclic nucleotide-related targets involved in the control of the function of the bladder, prostate, and urethra and the significance of those proteins in the process of evolving new pharmacological options for the treatment of LUT symptoms secondary to benign prostatic hyperplasia as well as dysfunctions of the storage and voiding capability of the urinary bladder. SN - 0171-2004 UR - https://www.unboundmedicine.com/medline/citation/21290241/Cyclic_nucleotide_metabolism_including_nitric_oxide_and_phosphodiesterase_related_targets_in_the_lower_urinary_tract_ L2 - https://dx.doi.org/10.1007/978-3-642-16499-6_23 DB - PRIME DP - Unbound Medicine ER -