Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium

Donna Sellers, Russ Chess-Williams, Martin C. Michel*

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

4 Citations (Scopus)
92 Downloads (Pure)

Abstract

The epithelial inner layer of the lower urinary tract, i.e., the urothelium, and other parts of the mucosa are not just a passive barrier but play an active role in the sensing of stretching, neurotransmitters, paracrine mediators, hormones, and growth factors and of changes in the extracellular environment. We review the molecular and cellular mechanisms enabling the urothelium to sense such inputs and how this leads to modulation of smooth muscle contraction and relaxation. The urothelium releases various mediators including ATP, acetylcholine, prostaglandins, nitric oxide, and nerve growth factor. These may affect function and growth of smooth muscle cells and afferent nerves. However, the molecular identity of the urothelium-derived mediator directly modulating contractile and relaxant responses of isolated bladder strips has remained elusive. The morphology and function of the urothelium undergo changes with aging and in many pathophysiological conditions. Therefore, the urothelium may contribute to the therapeutic effects of established drugs to treat lower urinary tract dysfunction and may also serve as a target for novel therapeutics. However, therapeutics may also change urothelial function, and it is not always easy to determine whether such changes are part of the therapeutic response or reflect secondary alterations.

Original languageEnglish
Pages (from-to)675-694
Number of pages20
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume391
Issue number7
Early online date28 May 2018
DOIs
Publication statusPublished - Jul 2018

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Urothelium
Muscle Relaxation
Muscle Contraction
Urinary Tract
Smooth Muscle
Therapeutic Uses
Nerve Growth Factor
Acetylcholine
Prostaglandins
Smooth Muscle Myocytes
Neurotransmitter Agents
Intercellular Signaling Peptides and Proteins
Nitric Oxide
Mucous Membrane
Urinary Bladder
Therapeutics
Adenosine Triphosphate
Hormones
Growth
Pharmaceutical Preparations

Cite this

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abstract = "The epithelial inner layer of the lower urinary tract, i.e., the urothelium, and other parts of the mucosa are not just a passive barrier but play an active role in the sensing of stretching, neurotransmitters, paracrine mediators, hormones, and growth factors and of changes in the extracellular environment. We review the molecular and cellular mechanisms enabling the urothelium to sense such inputs and how this leads to modulation of smooth muscle contraction and relaxation. The urothelium releases various mediators including ATP, acetylcholine, prostaglandins, nitric oxide, and nerve growth factor. These may affect function and growth of smooth muscle cells and afferent nerves. However, the molecular identity of the urothelium-derived mediator directly modulating contractile and relaxant responses of isolated bladder strips has remained elusive. The morphology and function of the urothelium undergo changes with aging and in many pathophysiological conditions. Therefore, the urothelium may contribute to the therapeutic effects of established drugs to treat lower urinary tract dysfunction and may also serve as a target for novel therapeutics. However, therapeutics may also change urothelial function, and it is not always easy to determine whether such changes are part of the therapeutic response or reflect secondary alterations.",
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Modulation of lower urinary tract smooth muscle contraction and relaxation by the urothelium. / Sellers, Donna; Chess-Williams, Russ; Michel, Martin C.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 391, No. 7, 07.2018, p. 675-694.

Research output: Contribution to journalReview articleResearchpeer-review

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AU - Michel, Martin C.

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AB - The epithelial inner layer of the lower urinary tract, i.e., the urothelium, and other parts of the mucosa are not just a passive barrier but play an active role in the sensing of stretching, neurotransmitters, paracrine mediators, hormones, and growth factors and of changes in the extracellular environment. We review the molecular and cellular mechanisms enabling the urothelium to sense such inputs and how this leads to modulation of smooth muscle contraction and relaxation. The urothelium releases various mediators including ATP, acetylcholine, prostaglandins, nitric oxide, and nerve growth factor. These may affect function and growth of smooth muscle cells and afferent nerves. However, the molecular identity of the urothelium-derived mediator directly modulating contractile and relaxant responses of isolated bladder strips has remained elusive. The morphology and function of the urothelium undergo changes with aging and in many pathophysiological conditions. Therefore, the urothelium may contribute to the therapeutic effects of established drugs to treat lower urinary tract dysfunction and may also serve as a target for novel therapeutics. However, therapeutics may also change urothelial function, and it is not always easy to determine whether such changes are part of the therapeutic response or reflect secondary alterations.

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