Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder

Sylvia O. Suadicani, Marcia Urban-Maldonado, Moses T. Tar, Arnold Melman, David C. Spray

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38 Citations (Scopus)

Abstract

OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X 1R, and increase in P2X 7R expression. There was decreased Cx43 and increased P2Y 4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X 1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y 4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y 2R, P2X 4R and increase in P2X 1R expression in the corpora, and by a doubling in Cx43 and P2Y 2R, and significant increase in P2Y 4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

Original languageEnglish (US)
Pages (from-to)1686-1693
Number of pages8
JournalBJU International
Volume103
Issue number12
DOIs
StatePublished - Jun 2009

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Purinergic P2 Receptors
Connexin 43
Experimental Diabetes Mellitus
Urinary Bladder
Erectile Dysfunction
Connexins
Insulin
Purinergic Receptors
Gap Junctions
Inbred F344 Rats
Streptozocin
Diabetes Mellitus
Proteins
Western Blotting

Keywords

  • Ageing
  • Bladder dysfunction
  • Connexin43
  • Diabetes mellitus
  • Erectile dysfunction
  • P2 receptors

ASJC Scopus subject areas

  • Urology

Cite this

@article{507afdce7a5d43c0924582a6eb56bbe1,
title = "Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder",
abstract = "OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X 1R, and increase in P2X 7R expression. There was decreased Cx43 and increased P2Y 4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X 1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y 4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y 2R, P2X 4R and increase in P2X 1R expression in the corpora, and by a doubling in Cx43 and P2Y 2R, and significant increase in P2Y 4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.",
keywords = "Ageing, Bladder dysfunction, Connexin43, Diabetes mellitus, Erectile dysfunction, P2 receptors",
author = "Suadicani, {Sylvia O.} and Marcia Urban-Maldonado and Tar, {Moses T.} and Arnold Melman and Spray, {David C.}",
year = "2009",
month = "6",
doi = "10.1111/j.1464-410X.2008.08337.x",
language = "English (US)",
volume = "103",
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TY - JOUR

T1 - Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder

AU - Suadicani, Sylvia O.

AU - Urban-Maldonado, Marcia

AU - Tar, Moses T.

AU - Melman, Arnold

AU - Spray, David C.

PY - 2009/6

Y1 - 2009/6

N2 - OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X 1R, and increase in P2X 7R expression. There was decreased Cx43 and increased P2Y 4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X 1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y 4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y 2R, P2X 4R and increase in P2X 1R expression in the corpora, and by a doubling in Cx43 and P2Y 2R, and significant increase in P2Y 4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

AB - OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X 1R, and increase in P2X 7R expression. There was decreased Cx43 and increased P2Y 4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X 1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y 4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y 2R, P2X 4R and increase in P2X 1R expression in the corpora, and by a doubling in Cx43 and P2Y 2R, and significant increase in P2Y 4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

KW - Ageing

KW - Bladder dysfunction

KW - Connexin43

KW - Diabetes mellitus

KW - Erectile dysfunction

KW - P2 receptors

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DO - 10.1111/j.1464-410X.2008.08337.x

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