Contractile properties of the pig bladder mucosa in response to neurokinin A: A role for myofibroblasts?

P. Sadananda, R. Chess-Williams, E. Burcher

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Abstract

Background and purpose: The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. Experimental approach: Discrete concentration-response curves for carbachol and NKA were obtained in matched strips of porcine detrusor, mucosa and intact bladder, suspended in organ baths. The effects of inhibitors and tachykinin receptor antagonists were studied on NKA-mediated contractions in mucosal strips. Intact sections of bladder and experimental strips were processed for histology and immunohistochemistry. Key results: All types of strips contracted to both carbachol and NKA. Mucosal responses to NKA (pD 2 7.2) were higher than those in intact strips and were inhibited by the NK 2 receptor antagonist SR48968 (pK B 9.85) but not the NK 1 receptor antagonist SR140333, tetrodotoxin or indomethacin. Immunostaining for smooth muscle actin and vimentin occurred under the urothelium and on blood vessels. Desmin immunostaining and histological studies showed only sparse smooth muscle to be present in the mucosal strips. Removal of smooth muscle remnants from mucosal strips did not alter the responses to NKA. Conclusions and implications: This study has shown both functional and histological evidence for contractile properties of the mucosa, distinct from the detrusor. Mucosal contractions to NKA appear to be directly mediated via NK 2 receptors. The main cell type mediating mucosal contractions is suggested to be suburothelial myofibroblasts. Mucosal contractions may be important in vivo for matching the luminal surface area to bladder volume.

Original languageEnglish
Pages (from-to)1465-1473
Number of pages9
JournalBritish Journal of Pharmacology
Volume153
Issue number7
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Neurokinin A
Myofibroblasts
Mucous Membrane
Urinary Bladder
Swine
Carbachol
Neurokinin-2 Receptors
Smooth Muscle
Urothelium
Tachykinin Receptors
Neurokinin-1 Receptors
Tachykinins
Desmin
Tetrodotoxin
Vimentin
Baths
Indomethacin
Blood Vessels
Actins
Histology

Cite this

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title = "Contractile properties of the pig bladder mucosa in response to neurokinin A: A role for myofibroblasts?",
abstract = "Background and purpose: The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. Experimental approach: Discrete concentration-response curves for carbachol and NKA were obtained in matched strips of porcine detrusor, mucosa and intact bladder, suspended in organ baths. The effects of inhibitors and tachykinin receptor antagonists were studied on NKA-mediated contractions in mucosal strips. Intact sections of bladder and experimental strips were processed for histology and immunohistochemistry. Key results: All types of strips contracted to both carbachol and NKA. Mucosal responses to NKA (pD 2 7.2) were higher than those in intact strips and were inhibited by the NK 2 receptor antagonist SR48968 (pK B 9.85) but not the NK 1 receptor antagonist SR140333, tetrodotoxin or indomethacin. Immunostaining for smooth muscle actin and vimentin occurred under the urothelium and on blood vessels. Desmin immunostaining and histological studies showed only sparse smooth muscle to be present in the mucosal strips. Removal of smooth muscle remnants from mucosal strips did not alter the responses to NKA. Conclusions and implications: This study has shown both functional and histological evidence for contractile properties of the mucosa, distinct from the detrusor. Mucosal contractions to NKA appear to be directly mediated via NK 2 receptors. The main cell type mediating mucosal contractions is suggested to be suburothelial myofibroblasts. Mucosal contractions may be important in vivo for matching the luminal surface area to bladder volume.",
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Contractile properties of the pig bladder mucosa in response to neurokinin A : A role for myofibroblasts? / Sadananda, P.; Chess-Williams, R.; Burcher, E.

In: British Journal of Pharmacology, Vol. 153, No. 7, 04.2008, p. 1465-1473.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - A role for myofibroblasts?

AU - Sadananda, P.

AU - Chess-Williams, R.

AU - Burcher, E.

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N2 - Background and purpose: The bladder urothelium is now known to have active properties. Our aim was to investigate the contractile properties of the urinary mucosa in response to the tachykinin neurokinin A (NKA) and carbachol. Experimental approach: Discrete concentration-response curves for carbachol and NKA were obtained in matched strips of porcine detrusor, mucosa and intact bladder, suspended in organ baths. The effects of inhibitors and tachykinin receptor antagonists were studied on NKA-mediated contractions in mucosal strips. Intact sections of bladder and experimental strips were processed for histology and immunohistochemistry. Key results: All types of strips contracted to both carbachol and NKA. Mucosal responses to NKA (pD 2 7.2) were higher than those in intact strips and were inhibited by the NK 2 receptor antagonist SR48968 (pK B 9.85) but not the NK 1 receptor antagonist SR140333, tetrodotoxin or indomethacin. Immunostaining for smooth muscle actin and vimentin occurred under the urothelium and on blood vessels. Desmin immunostaining and histological studies showed only sparse smooth muscle to be present in the mucosal strips. Removal of smooth muscle remnants from mucosal strips did not alter the responses to NKA. Conclusions and implications: This study has shown both functional and histological evidence for contractile properties of the mucosa, distinct from the detrusor. Mucosal contractions to NKA appear to be directly mediated via NK 2 receptors. The main cell type mediating mucosal contractions is suggested to be suburothelial myofibroblasts. Mucosal contractions may be important in vivo for matching the luminal surface area to bladder volume.

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