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Aging changes agonist induced contractile responses in permeabilized rat bladder

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Abstract

Aging alters bladder functions where a decrease in filling, storage and emptying is observed. These changes cause urinary incontinence, especially in women. The aim of this study is to examine how aging affects the intracellular calcium movements due to agonist-induced contractions in permeabilized female rat bladder. Urinary bladder isolated from young and old female Sprague-Dawley rats were used. Small detrusor strips were permeabilized with β-escin. The contractile responses induced with agonists were compared between young and old groups. Carbachol-induced contractions were decreased in permeabilized detrusor from old rats compared to young group. Heparin and ryanodine decreased carbachol-induced contractions in young rats where only heparin inhibited these contractions in olds. Caffeine-induced contractions but not inositol triphosphate (IP3)-induced contractions were decreased in old group compared to youngs. The cumulative calcium response curves (pCa 8–4) were also decreased in old rats. Carbachol-induced calcium sensitization responses did not alter by age where GTP-β-S and GF-109203X but not Y-27632 inhibited these responses. Carbachol-induced contractions decrease with aging in rat bladder detrusor. It can be postulated as IP3-induced calcium release (IICR) is primarily responsible for the contractions in older rats where the decrease in carbachol contractions in aging may be as a result of a decrease in calcium-induced calcium release (CICR), rather than carbachol-induced calcium sensitization.

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References

  • Anderson KE (1993) Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 45(3):253–308

    CAS  PubMed  Google Scholar 

  • Belibi FA, Wallace DP, Yamaguchi T, Christensen M, Reif G, Grantham JJ (2002) The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol JASN 13(11):2723–2729

    Article  CAS  PubMed  Google Scholar 

  • Bing W, Chang S, Hypolite JA, DiSanto ME, Zderic SA, Rolf L, Wein AJ, Chacko S (2003) Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol Ren Physiol 285(5):F990–F997

    Article  Google Scholar 

  • Brooks SP, Storey KB (1992) Bound and determined: a computer program for making buffers of defined ion concentrations. Anal Biochem 201:119–126

  • Chambers P, Neal DE, Gillespie JI (1999) Ryanodine receptors in human bladder smooth muscle. Exp Physiol 84(1):41–46

    Article  CAS  PubMed  Google Scholar 

  • de Groat WC, Yoshimura N (2001) Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol 41:691–721

    Article  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(3):969–974

    CAS  PubMed  Google Scholar 

  • Durlu-Kandilci NT, Brading AF (2006) Involvement of Rho kinase and protein kinase C in carbachol-induced calcium sensitization in beta-escin skinned rat and guinea-pig bladders. Br J Pharmacol 148(3):376–384

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Endo MKT, Yagi S, Iino M, Kakuta Y (1977) Some properties of chemically skinned smooth muscle fibers. In: Casteels R et al (eds) Excitation-contraction coupling in smooth muscle. Elsevier, Amsterdam, pp 199–209

    Google Scholar 

  • Endo M, Yagi S, Iino M (1982) Tension-pCa relation and sarcoplasmic reticulum responses in chemically skinned smooth muscle fibers. Fed Proc 41(7):2245–2250

    CAS  PubMed  Google Scholar 

  • Gomez-Pinilla PJ, Pozo MJ, Camello PJ (2011) Aging differentially modifies agonist-evoked mouse detrusor contraction and calcium signals. Age (Dordr) 33(1):81–88

    Article  CAS  Google Scholar 

  • Hashim H, Abrams P (2007) Overactive bladder: an update. Curr Opin Urol 17(4):231–236

    Article  PubMed  Google Scholar 

  • Iizuka K, Ikebe M, Somlyo AV, Somlyo AP (1994) Introduction of high molecular weight (IgG) proteins into receptor coupled, permeabilized smooth muscle. Cell Calcium 16(6):431–445

    Article  CAS  PubMed  Google Scholar 

  • Kaneda T, Shimizu K, Nakajyo S, Urakawa N (1995) Effect of phorbol ester, 12-deoxyphorbol 13-isobutylate (DPB), on muscle tension and cytosolic Ca2+ in rat anococcygeus muscle. Jpn J Pharmacol 69(3):195–204

    Article  CAS  PubMed  Google Scholar 

  • Kirschstein T, Protzel C, Porath K, Sellmann T, Kohling R, Hakenberg OW (2014) Age-dependent contribution of Rho kinase in carbachol-induced contraction of human detrusor smooth muscle in vitro. Acta Pharmacol Sin 35(1):74–81

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kitazawa T, Kobayashi S, Horiuti K, Somlyo AV, Somlyo AP (1989) Receptor-coupled, permeabilized smooth muscle. Role of the phosphatidylinositol cascade, G-proteins, and modulation of the contractile response to Ca2+. J Biol Chem 264(10):5339–5342

    CAS  PubMed  Google Scholar 

  • Kobayashi S, Kitazawa T, Somlyo AV, Somlyo AP (1989) Cytosolic heparin inhibits muscarinic and alpha-adrenergic Ca2+ release in smooth muscle. Physiological role of inositol 1,4,5-trisphosphate in pharmacomechanical coupling. J Biol Chem 264(30):17997–18004

    CAS  PubMed  Google Scholar 

  • Lindaman BA, Hinkhouse MM, Conklin JL, Cullen JJ (2002) The effect of phosphodiesterase inhibition on gallbladder motility in vitro. J Surg Res 105(2):102–108

    Article  CAS  PubMed  Google Scholar 

  • Lluel P, Palea S, Barras M, Grandadam F, Heudes D, Bruneval P, Corman B, Martin DJ (2000) Functional and morphological modifications of the urinary bladder in aging female rats. Am J Physiol Regul Integr Comp Physiol 278(4):R964–R972

    CAS  PubMed  Google Scholar 

  • Lowalekar SK, Cristofaro V, Radisavljevic ZM, Yalla SV, Sullivan MP (2012) Loss of bladder smooth muscle caveolae in the aging bladder. Neurourol Urodyn 31(4):586–592

    Article  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(8):1089–1099

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nasu T (1989) Actions of some drugs on skinned smooth muscle preparations. Gen Pharmacol 20(2):123–131

    Article  CAS  PubMed  Google Scholar 

  • Ordway GA, Esbenshade TA, Kolta MG, Gerald MC, Wallace LJ (1986) Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder. J Urol 136(2):492–496

    CAS  PubMed  Google Scholar 

  • Schneider T, Hein P, Michel-Reher MB, Michel M (2005) Effects of ageing on muscarinic receptor subtypes and function in rat urinary bladder. N-S Arch Pharmacol 372(1):71–78

    Article  CAS  Google Scholar 

  • Sjuve R, Uvelius B, Arner A (1997) Old age does not affect shortening velocity or content of contractile and cytoskeletal proteins in the rat detrusor smooth muscle. Urol Res 25(1):67–70

    Article  CAS  PubMed  Google Scholar 

  • Smith PP (2010) Aging and the underactive detrusor: a failure of activity or activation? Neurourol Urodyn 29(3):408–412

    PubMed  Google Scholar 

  • Somlyo AV (2002) New roads leading to Ca2+ sensitization. Circ Res 91(2):83–84

    Article  CAS  PubMed  Google Scholar 

  • Somlyo AP, Himpens B (1989) Cell calcium and its regulation in smooth muscle. FASEB J Off Publ Fed Am Soc Exp Biol 3(11):2266–2276

    CAS  Google Scholar 

  • Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83(4):1325–1358

    Article  CAS  PubMed  Google Scholar 

  • Takahashi R, Nishimura J, Hirano K, Seki N, Naito S, Kanaide H (2004) Ca(2+) sensitization in contraction of human bladder smooth muscle. J Urol 172(2):748–752

    Article  CAS  PubMed  Google Scholar 

  • Tugba Durlu-Kandilci N, Brading AF (2007) Intracellular calcium stores in beta-escin skinned rat and guinea-pig bladders. Eur J Pharmacol 566(1-3):172–180

    Article  CAS  PubMed  Google Scholar 

  • Volpe P, Salviati G, Chu A (1986) Calcium-gated calcium channels in sarcoplasmic reticulum of rabbit skinned skeletal muscle fibers. J Gen Physiol 87(2):289–303

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wibberley A, Chen Z, Hu E, Hieble JP, Westfall TD (2003) Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle. Br J Pharmacol 138(5):757–766

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wibo M, Godfraind T (1994) Comparative localization of inositol 1,4,5-trisphosphate and ryanodine receptors in intestinal smooth muscle: an analytical subfractionation study. Biochem J 297(Pt 2):415–423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao W, Aboushwareb T, Turner C, Mathis C, Bennett C, Sonntag WE, Andersson KE, Christ G (2010) Impaired bladder function in aging male rats. J Urol 184(1):378–385

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This study was supported by 2012 L’Oreal Turkey “Women in Science” Grants (NT Durlu-Kandilci).

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmacology, Hacettepe University, 06100, Sıhhiye, Ankara, Turkey

    N. Tugba Durlu-Kandilci, Merve Denizalti & Inci Sahin-Erdemli

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  1. N. Tugba Durlu-Kandilci
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  2. Merve Denizalti
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  3. Inci Sahin-Erdemli
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Correspondence to N. Tugba Durlu-Kandilci.

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Durlu-Kandilci, N.T., Denizalti, M. & Sahin-Erdemli, I. Aging changes agonist induced contractile responses in permeabilized rat bladder. AGE 37, 69 (2015). https://doi.org/10.1007/s11357-015-9807-8

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  • DOI: https://doi.org/10.1007/s11357-015-9807-8

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