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Melatonin restores impaired contractility in aged guinea pig urinary bladder

Gomez-Pinilla, Pedro J; Gomez, Maria LU ; Swärd, Karl LU ; Hedlund, Petter LU ; Hellstrand, Per LU ; Camello, Pedro J; Andersson, Karl-Erik LU and Pozo, Maria J (2008) In Journal of Pineal Research 44(4). p.416-425
Abstract
Urinary bladder disturbances are frequent in the elderly population but the responsible mechanisms are poorly understood. This study evaluates the effects of aging on detrusor myogenic contractile responses and the impact of melatonin treatment. The contractility of bladder strips from adult, aged and melatonin-treated guinea pigs was evaluated by isometric tension recordings. Cytoplasmatic calcium concentration ([Ca2+](i)) was estimated by epifluorescence microscopy of fura-2-loaded isolated detrusor smooth muscle cells, and the levels of protein expression and phosphorylation were quantitated by Western blotting. Aging impairs the contractile response of detrusor strips to cholinergic and purinergic agonists and to membrane... (More)
Urinary bladder disturbances are frequent in the elderly population but the responsible mechanisms are poorly understood. This study evaluates the effects of aging on detrusor myogenic contractile responses and the impact of melatonin treatment. The contractility of bladder strips from adult, aged and melatonin-treated guinea pigs was evaluated by isometric tension recordings. Cytoplasmatic calcium concentration ([Ca2+](i)) was estimated by epifluorescence microscopy of fura-2-loaded isolated detrusor smooth muscle cells, and the levels of protein expression and phosphorylation were quantitated by Western blotting. Aging impairs the contractile response of detrusor strips to cholinergic and purinergic agonists and to membrane depolarization. The impaired contractility correlates with increased [Ca2+](i) in response to the stimuli, suggesting a reduced Ca(2+)sensitivity. Indeed, the agonist-induced contractions in adult strips were sensitive to blockade with Y27362, an inhibitor of Rho kinase (ROCK) and GF109203X, an inhibitor of protein kinase C (PKC), but these inhibitors had negligible effects in aged strips. The reduced Ca2+ sensitivity in aged tissues correlated with lower levels of RhoA, ROCK, PKC and the two effectors CPI-17 and MYPT1, and with the absence of CPI-17 and MYPT1 phosphorylation in response to agonists. Interestingly, melatonin treatment restored impaired contractility via normalization of Ca2+ handling and Ca2+ sensitizations pathways. Moreover, the indoleamine restored age-induced changes in oxidative stress and mitochondrial polarity. These results suggest that melatonin might be a novel therapeutic tool to palliate aging-related urinary bladder contractile impairment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
melatonin, guinea pig, calcium signalling, aging, calcium sensitization, mitochondria, urinary bladder
in
Journal of Pineal Research
volume
44
issue
4
pages
416 - 425
publisher
Wiley-Blackwell
external identifiers
  • wos:000254953700010
  • scopus:42149134420
ISSN
1600-079X
DOI
10.1111/j.1600-079X.2007.00544.x
language
English
LU publication?
yes
id
b77d1280-4379-4bee-9ccc-925fb87de454 (old id 1206328)
date added to LUP
2008-09-19 12:36:27
date last changed
2017-04-09 03:39:37
@article{b77d1280-4379-4bee-9ccc-925fb87de454,
  abstract     = {Urinary bladder disturbances are frequent in the elderly population but the responsible mechanisms are poorly understood. This study evaluates the effects of aging on detrusor myogenic contractile responses and the impact of melatonin treatment. The contractility of bladder strips from adult, aged and melatonin-treated guinea pigs was evaluated by isometric tension recordings. Cytoplasmatic calcium concentration ([Ca2+](i)) was estimated by epifluorescence microscopy of fura-2-loaded isolated detrusor smooth muscle cells, and the levels of protein expression and phosphorylation were quantitated by Western blotting. Aging impairs the contractile response of detrusor strips to cholinergic and purinergic agonists and to membrane depolarization. The impaired contractility correlates with increased [Ca2+](i) in response to the stimuli, suggesting a reduced Ca(2+)sensitivity. Indeed, the agonist-induced contractions in adult strips were sensitive to blockade with Y27362, an inhibitor of Rho kinase (ROCK) and GF109203X, an inhibitor of protein kinase C (PKC), but these inhibitors had negligible effects in aged strips. The reduced Ca2+ sensitivity in aged tissues correlated with lower levels of RhoA, ROCK, PKC and the two effectors CPI-17 and MYPT1, and with the absence of CPI-17 and MYPT1 phosphorylation in response to agonists. Interestingly, melatonin treatment restored impaired contractility via normalization of Ca2+ handling and Ca2+ sensitizations pathways. Moreover, the indoleamine restored age-induced changes in oxidative stress and mitochondrial polarity. These results suggest that melatonin might be a novel therapeutic tool to palliate aging-related urinary bladder contractile impairment.},
  author       = {Gomez-Pinilla, Pedro J and Gomez, Maria and Swärd, Karl and Hedlund, Petter and Hellstrand, Per and Camello, Pedro J and Andersson, Karl-Erik and Pozo, Maria J},
  issn         = {1600-079X},
  keyword      = {melatonin,guinea pig,calcium signalling,aging,calcium sensitization,mitochondria,urinary bladder},
  language     = {eng},
  number       = {4},
  pages        = {416--425},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Pineal Research},
  title        = {Melatonin restores impaired contractility in aged guinea pig urinary bladder},
  url          = {http://dx.doi.org/10.1111/j.1600-079X.2007.00544.x},
  volume       = {44},
  year         = {2008},
}