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Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals

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Abstract

Although aging-induced changes in urinary bladder neurotransmission have been studied in some detail, information regarding alterations in detrusor muscle is scanty and addresses only partial aspects of the myogenic response of detrusor. Rodent bladder aging shows several features similar to those reported in humans. The aim of this study was to characterize in aged mouse the alterations of detrusor muscle contraction and the putative underlying changes in Ca2+ signals. We studied in vitro the myogenic contraction induced by agonists in detrusor strips from adult (3 months old) or aged (23–25 months old) mice. In addition, we determined the agonist-induced [Ca2+]i signals by epifluorescence microscopy in fura-2 loaded isolated detrusor cells. Aging impaired the contractile response of bladder strips to cholinergic stimulation with bethanechol and to chemical depolarization with KCl-containing solutions. On the contrary, the response to purinergic stimulation (ATP) was enhanced. Aging also diminished the transient Ca2+ signal evoked by bethanechol and the Ca2+ influx induced by KCl in bladder strips. Treatments aimed to release calcium from intracellular stores (caffeine and a low level of ionomycin in Ca2+-free medium) showed that aging reduces the size of agonist-releasable stores. Similar to contraction, the mobilization of Ca2+ by ATP was increased in aged cells. Therefore, the differential effects of aging on detrusor contraction are associated to alterations of [Ca2+]i signals: the cholinergic inhibition is due to inhibition of voltage-operated Ca2+ influx and reduction of the size of intracellular Ca2+ stores, while the age-induced ATP response is accompanied by an enhanced Ca2+ mobilization.

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References

  • Camello-Almaraz C, Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2008) Age-related alterations in Ca2+ signals and mitochondrial membrane potential in exocrine cells are prevented by melatonin. J Pineal Res 45:191–198

    Article  CAS  PubMed  Google Scholar 

  • Camello-Almaraz C, Macias B, Gomez-Pinilla PJ, Alcon S, Martin-Cano FE, Baba A, Matsuda T, Camello PJ, Pozo MJ (2009) Developmental changes in Ca2+ homeostasis and contractility in gallbladder smooth muscle. Am J Physiol Cell Physiol 296:C783–C791

    Article  CAS  PubMed  Google Scholar 

  • Derweesh IH, Wheeler MA, Weiss RM (2000) Alterations in G-proteins and beta-adrenergic responsive adenylyl cyclase in rat urinary bladder during aging. J Pharmacol Exp Ther 294:969–974

    CAS  PubMed  Google Scholar 

  • Diokno AC, Brown MB, Goldstein N, Herzog AR (1992) Epidemiology of bladder emptying symptoms in elderly men. J Urol 148:1817–1821

    CAS  PubMed  Google Scholar 

  • Ford AP, Gever JR, Nunn PA, Zhong Y, Cefalu JS, Dillon MP, Cockayne DA (2006) Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol 147(Suppl 2):S132–S143

    Article  CAS  PubMed  Google Scholar 

  • Fry CH, Skennerton D, Wood D, Wu C (2002) The cellular basis of contraction in human detrusor smooth muscle from patients with stable and unstable bladders. Urology 59:3–12

    Article  PubMed  Google Scholar 

  • Gomez-Pinilla PJ, Gomez MF, Hedlund P, Sward K, Hellstrand P, Camello PJ, Pozo MJ, Andersson KE (2007a) Effect of melatonin on age associated changes in Guinea pig bladder function. J Urol 177:1558–1561

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Pinilla PJ, Pozo MJ, Baba A, Matsuda T, Camello PJ (2007b) Ca2+ extrusion in aged smooth muscle cells. Biochem Pharmacol 74:860–869

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2007c) Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin. Am J Physiol Regul Integr Comp Physiol 293:R793–R803

    CAS  PubMed  Google Scholar 

  • Gomez-Pinilla PJ, Gomez MF, Sward K, Hedlund P, Hellstrand P, Camello PJ, Andersson KE, Pozo MJ (2008) Melatonin restores impaired contractility in aged guinea pig urinary bladder. J Pineal Res 44:416–425

    Article  CAS  PubMed  Google Scholar 

  • Harvey RA, Skennerton DE, Newgreen D, Fry CH (2002) The contractile potency of adenosine triphosphate and ecto-adenosine triphosphatase activity in guinea pig detrusor and detrusor from patients with a stable, unstable or obstructed bladder. J Urol 168:1235–1239

    Article  CAS  PubMed  Google Scholar 

  • Hashitani H, Fukuta H, Takano H, Klemm MF, Suzuki H (2001) Origin and propagation of spontaneous excitation in smooth muscle of the guinea-pig urinary bladder. J Physiol 530:273–286

    Article  CAS  PubMed  Google Scholar 

  • Heppner TJ, Bonev AD, Nelson MT (2005) Elementary purinergic Ca2+ transients evoked by nerve stimulation in rat urinary bladder smooth muscle. J Physiol 564:201–212

    Article  CAS  PubMed  Google Scholar 

  • Iacovou JW, Hill SJ, Birmingham AT (1990) Agonist-induced contraction and accumulation of inositol phosphates in the guinea-pig detrusor: evidence that muscarinic and purinergic receptors raise intracellular calcium by different mechanisms. J Urol 144:775–779

    CAS  PubMed  Google Scholar 

  • Kageyama S, Fujita K, Suzuki K, Shinbo H, Masuda N, Uchida W (2000) Effect of age on the responses of rat bladder detrusor strips to adenosine triphosphate. BJU Int 85:899–904

    Article  CAS  PubMed  Google Scholar 

  • Kajioka S, Nakayama S, Asano H, Brading AF (2005) Involvement of ryanodine receptors in muscarinic receptor-mediated membrane current oscillation in urinary bladder smooth muscle. Am J Physiol Cell Physiol 288:C100–C108

    CAS  PubMed  Google Scholar 

  • Lieu PK, Sa'adu A, Orugun EO, Malone-Lee JG (1997) The influence of age on isometric and isotonic rat detrusor contractions. J Gerontol A Biol Sci Med Sci 52:M94–M96

    CAS  PubMed  Google Scholar 

  • Lin AT, Hsu TH, Yang C, Chang LS (2000) Effects of aging on mitochondrial enzyme activity of rat urinary bladder. Urol Int 65:144–147

    Article  CAS  PubMed  Google Scholar 

  • Lluel P, Palea S, Ribiere P, Barras M, Teillet L, Corman B (2003) Increased adrenergic contractility and decreased mRNA expression of NOS III in aging rat urinary bladders. Fundam Clin Pharmacol 17:633–641

    Article  CAS  PubMed  Google Scholar 

  • Mansfield KJ, Liu L, Mitchelson FJ, Moore KH, Millard RJ, Burcher E (2005) Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. Br J Pharmacol 144:1089–1099

    Article  CAS  PubMed  Google Scholar 

  • Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ (2001) How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 87:760–766

    Article  CAS  PubMed  Google Scholar 

  • Morales S, Camello PJ, Alcon S, Salido GM, Mawe G, Pozo MJ (2004) Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder. Am J Physiol Gastrointest Liver Physiol 286:G1090–G1100

    Article  CAS  PubMed  Google Scholar 

  • Nishimoto T, Latifpour J, Wheeler MA, Yoshida M, Weiss RM (1995) Age-dependent alterations in beta-adrenergic responsiveness of rat detrusor smooth muscle. J Urol 153:1701–1705

    Article  CAS  PubMed  Google Scholar 

  • Pagala MK, Tetsoti L, Nagpal D, Wise GJ (2001) Aging effects on contractility of longitudinal and circular detrusor and trigone of rat bladder. J Urol 166:721–727

    Article  CAS  PubMed  Google Scholar 

  • Saito M, Kondo A, Gotoh M, Kato K, Levin RM (1993) Age-related changes in the response of the rat urinary bladder to neurotransmitters. Neurourol Urodyn 12:191–200

    Article  CAS  PubMed  Google Scholar 

  • Schneider T, Hein P, Michel-Reher MB, Michel MC (2005) Effects of ageing on muscarinic receptor subtypes and function in rat urinary bladder. Naunyn Schmiedebergs Arch Pharmacol 372:71–78

    Article  CAS  PubMed  Google Scholar 

  • Siroky MB (2004) The aging bladder. Rev Urol 6(Suppl 1):S3–S7

    PubMed  Google Scholar 

  • Suadicani SO, Urban-Maldonado M, Tar MT, Melman A, Spray DC (2009) Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder. BJU Int 103:1686–1693

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y, Moriyama N, Kanada A, Okaya Y, Kawabe K, Aisaka K (1999) The role of alpha 1 L-adrenoceptor in rat urinary bladder: comparison between young adult and aged rats. Life Sci 65:2553–2559

    Article  CAS  PubMed  Google Scholar 

  • Toescu EC, Verkhratsky A (2000) Parameters of calcium homeostasis in normal neuronal ageing. J Anat 197(Pt 4):563–569

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Bayliss M, Newgreen D, Mundy AR, Fry CH (1999) A comparison of the mode of action of ATP and carbachol on isolated human detrusor smooth muscle. J Urol 162:1840–1847

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Sui G, Fry CH (2002) The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle. J Physiol 538:357–369

    Article  CAS  PubMed  Google Scholar 

  • Yoshida M, Homma Y, Inadome A, Yono M, Seshita H, Miyamoto Y, Murakami S, Kawabe K, Ueda S (2001) Age-related changes in cholinergic and purinergic neurotransmission in human isolated bladder smooth muscles. Exp Gerontol 36:99–109

    Article  CAS  PubMed  Google Scholar 

  • Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A (2004) Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63:17–23

    Article  PubMed  Google Scholar 

  • Young JS, Meng E, Cunnane TC, Brain KL (2008) Spontaneous purinergic neurotransmission in the mouse urinary bladder. J Physiol 586:5743–5755

    Article  CAS  PubMed  Google Scholar 

  • Yu HJ, Wein AJ, Levin RM (1996) Age-related differential susceptibility to calcium channel blocker and low calcium medium in rat detrusor muscle: response to field stimulation. Neurourol Urodyn 15:563–576

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Junta de Extremadura (PRI07A069) and Spanish Ministery of Science and Education (BFU 2007-60563) and Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad Grant RD06/0013/1012.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, 10071, Cáceres, Spain

    Pedro J. Gomez-Pinilla, Maria J. Pozo & Pedro J. Camello

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  1. Pedro J. Gomez-Pinilla
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  2. Maria J. Pozo
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  3. Pedro J. Camello
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Correspondence to Pedro J. Camello.

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Gomez-Pinilla, P.J., Pozo, M.J. & Camello, P.J. Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals. AGE 33, 81–88 (2011). https://doi.org/10.1007/s11357-010-9163-7

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  • DOI: https://doi.org/10.1007/s11357-010-9163-7

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