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G proteins, adenylyl cyclase and related phosphoproteins in the developing rat heart

  • Part I: Cardiac Development and Regulation
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Abstract

The postnatal alterations of the composition of a subunit isoforms (Giαc, G iα3 Goα, and Gqα of G proteins, the adenylyl cyclase activity as well as of cAMP-regulated phosphoproteins e.g. troponin and phospholamban were investigated in the ventricular tissue of 1, 7, 30 days old rats. Quantitative immunodetection revealed a 5.7-fold decrease in Giα3 at 30th postnatal day compared with the postnatal day 1 and up to 15-fold at 4 months. The amounts of Gqα and G∞ as well as the Gα subunits were found to be higher in the earlier life period compared to the adult. In contrast, the content of Gsα was uneffected by the developmental state. Basal adenylyl cyclase activity (pmoles cAMP/min × mg protein) increased from 30.9 ± 5.0, 36.8 ± 5.0 to 63.9 ± 5.9 at 1st, 7th and 30th postnatal day, respectively. Isoprenaline (100 μM) enhanced the activity of adenylyl cyclase from day 1, 7–30 from 46.2 ± 7.0, 79.1 ± 9.2 to 120.5 ± 7.2, respectively. The effects of forskolin and NaF on adenylyl cyclase activity was found to be not influenced within the first postnatal month. Furthermore, a developmentally controlled expression of cardiac troponin I was observed (6-fold from the first to the 28th postnatal day) whereas the level of phospholamban was found to be age-independent.

In conclusion, there is an increase in the efficiency of the β-adrenergic signal transfer mainly caused by a reduction of the inhibitiory G proteins and a dominance of the Gsα-linked pathway in the postnatal rat heart. Furthermore the developmentally controlled expression of troponin I might be of functional importance in the cAMP-supported relaxation. Additionally, altered Gqα, Goα and Gβ pattern of the developing rat ventricle may play a role in the observed change of α-adrenerg-mediated heart contractility as well as in cardiac differentiation and growth processes.

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References

  1. Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56; 615–649, 1987

    Article  PubMed  Google Scholar 

  2. McMahon KK: Developmental changes of the G proteins-muscarinic cholinergic receptor interactions in rat heart. J Pharmacol Exp Ther 251:372–377, 1989

    PubMed  Google Scholar 

  3. Brown AM: Regulation of heartbeat by G protein-coupled ion channels. Am J Physiol 259: H1621-H1628, 1990

    PubMed  Google Scholar 

  4. Karczewski P, Bartel S, Krause EG: Differential sensitivity to isoprenaline of troponin I and phospholamban phosphorylation in isolated rat hearts. Biochem J 266: 115–122, 1990

    PubMed  Google Scholar 

  5. Neer EJ, Clapham DE: Signal transduction through G proteins in the cardiac myocyte. Trends Cardiac Med 2: 6–11, 1992

    Article  Google Scholar 

  6. Eschenhagen T: G Proteins and the heart. Cell Biol International 17: 723–749, 1993

    Article  Google Scholar 

  7. Summers RJ, McMartin LR: Adrenoceptors and their second messenger systems. J Neurochem 60: 10–23, 1993

    PubMed  Google Scholar 

  8. Hadcock JR, Malbon CC: Agonist regulation of gene expression of adrenergic receptors and G proteins. J Neurochem 60: 1–9, 1993

    PubMed  Google Scholar 

  9. Luo W, Grupp IL, Harrer J, Ponniah S, Grupp D, Duffy T, Doetschmann K, Kranias EC: Target ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of β-agonist stimulation. Circ Res 75: 401–409, 1994

    PubMed  Google Scholar 

  10. Tobise K, Ishikawa Y, Holmer SR, Im MJ, Newell JB, Yoshie H, Fujita M, Susannie EE, CJ Homey: Changes in type VI adenylyl cyclase isoform expression correlate with a decreased capacity for cAMP generation in the ageing ventricle. Cite Res 74: 596–603, 1994

    Google Scholar 

  11. Mende U, Eschenhagen T, Geertz B, Schmitz W, Scholz H, Schulte am Esch J Sempell R, Steinfath M: Isoprenaline-induced increase in the 40/41 kDa pertusis toxin substrates and functional consequences on contractile response in rat heart. Naunyn Schmiedebergs Arch Pharmacol 345: 44–50, 1992

    PubMed  Google Scholar 

  12. Eschenhagen T, Mende U, Nose M, Schmitz W, Scholz H: Long-term β-adrenoceptor-mediated upregulation of Giα- and G -mRNA levels and pertussis toxin sensitive G-proteins in rat heart. Mol Pharmacol 42:773–783, 1992

    PubMed  Google Scholar 

  13. Eschenhagen T, Mende U, Nose M, Schmitz W, Scholz H, Haverich A, Hirt S, Döring V, Kalmar P, Hopper W, Seitz HJ: Increased messenger RNA level of the inhibitory G-protein α-subunit Giα-2 in human end-stage heart failure. Circ Res 70: 688–696, 1992

    PubMed  Google Scholar 

  14. Bristow MR, Ginsburg R, Minobe W, Cubiccioti RS, Sageman WS, Lurie K, Billingham MW, Harrison DC, Stinson EB: Decreased catecholamine sensitivity and beta-adrenergic receptor density in failing human heart. N Engl J Med 307: 205–211, 1982

    PubMed  Google Scholar 

  15. Feldman MD, Copeles L, Gwathmey JK, Philips P, Warren SE, Schoen FJ, Grossman W, Morgan JP: Deficient production of cyclic AMP: pharmacological evidence of an important cause of contractile dysfunction in patients with end-stage heart failure. Circulation 75: 331–339, 1987

    PubMed  Google Scholar 

  16. Feldman AM, Ray PE, Bristow MR: Expression of α-subunits of G proteins in failing human heart: a reappraisal utilizing polymerase chain reaction. J Mol Cell Cardiol 23: 439–452, 1991

    PubMed  Google Scholar 

  17. Neumann, Schmitz W, Scholz H, von Meyerinck L, Döring V, Kalmar P: Increase in myocardial Gi-proteins in human heart failure. Lancet 11: 936–937, 1988

    Article  Google Scholar 

  18. Böhm M, Gierschik P, Jakobs KH, Pieske B, Schnabel P, Ungerer M, Erdmann E: Increase of Giα in human hearts with dilated but not ischemic cardiomyopathy. Circulation 82: 1249–1265, 1990

    PubMed  Google Scholar 

  19. Kumar R, Joyner RW, Nartzell NC, Ellingsen D, Rishi F, Eaton DC, Lu C, Akita T: Postnatal changes in the G-proteins, cyclic nucleotides and adenylyl cyclase activity in rabbit heart cells. J Mol Cell Cardiol 26:1537–1550, 1994

    Article  PubMed  Google Scholar 

  20. Luetje CW, Tietje KM, Christian JL, Nathanson NM: Differential tissue expression and developmental regulation of guanine nucleotide binding regulatory proteins and their messenger RNAs in rat heart. J Biol Chem 263: 13357–13365, 1988

    PubMed  Google Scholar 

  21. Espinasse I, Iourgenko V, Defer N, Samson F, Hanoune J, Mercadier JJ: Type V, but not type VI, adenylyl cyclase mRNA accumulates in the rat heart during ontogenic development. Correlation with increased global adenylyl cyclase activity. J Mol Cell Cardiol 27: 1789–1795, 1995

    Article  PubMed  Google Scholar 

  22. Kaufman TM, Horton JW White DJ, Mahony L: Age-related changes in myocardial relaxation and sarcoplasmic reticulum. Am J Physiol 259: H309-H316, 1990

    PubMed  Google Scholar 

  23. Fischer PJ, Tate CA, Philipps S: Developmental regulation of the sarcoplasmic reticulum calcium pump in the rabbit heart. Pediatr Res 31: 474–479, 1992

    PubMed  Google Scholar 

  24. Szymanska G, Grupp IL, Slack JP, Harrer JM, Kranias EG: Alterations in sarcoplasmic reticulum calcium uptake, relaxation parameters and their responses to β-adrenergic agonists in the developing rabbit heart. J Mol Cell Cardiol 27: 1819–1829, 1995

    Article  PubMed  Google Scholar 

  25. Vetter R, Studer R, Reinecke H, Kolar F, Ostadalova I, Drexler H: Reciprocal changes in the post-natal expression of the sarcolemmal Na+-Ca2+ exchanger and SERCA2 in rat heart. J Mol Cell Cardiol 27: 1689–1701, 1995

    Article  PubMed  Google Scholar 

  26. Wattanapermpoll J, Guo X, Solaro RJ: The unique amino-terminal peptide of cardiac troponin I regulates myofibrillar activity only when it is phosphorylated. J Mol Cell Cardiol 27: 1383–1391, 1995

    Article  PubMed  Google Scholar 

  27. Artmann M, Kithas PA, Wike JS, Strada SJ: Inotropic responses during postnatal maturation in rabbit. Am J Physiol 255: H335-H342, 1988

    PubMed  Google Scholar 

  28. Martin AF, Ball K, Gao LZ, Kumar P, Solaro RJ: Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils. Circ Res 69: 1244–1252, 1991

    PubMed  Google Scholar 

  29. Bartel S, Morano I, Hunger HD, Katus H, Pask HT, Karczewski P, Krause EG: Cardiac troponin I and tension generation of skinned fibers in the developing rat heart. J Mol Cell Cardiol 26: 1123–1121, 1994

    Article  PubMed  Google Scholar 

  30. Lowry OH, Rosebrough NJ, Farr AC, Randell RJ: Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  31. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 277: 680–685, 1970

    Google Scholar 

  32. Will-Shahab L, Rosenthal W, Schulze W, Küttner I: G protein function in the ischemic myocardium. Eur Heart J 12: 135–138, 1991

    PubMed  Google Scholar 

  33. Saloman Y: Londos C, Rodbell MA: A highly sensitive adenylate cyclase assay. Anal Biochem 58: 541–548, 1974

    PubMed  Google Scholar 

  34. White AA, Zenser TV: Separation of cyclic 3′5′,-nucleotide monophosphates from other nucleotides on aluminium oxide columns. Analyt Biochem 43: 272–282, 1971

    Google Scholar 

  35. Fleming JW, Wisler PL, Watanabe AM: Signal transduction by G proteins on cardiac tissues. Circulation 85: 420–133, 1992

    PubMed  Google Scholar 

  36. Foster KA, McDermott PJ, Robishaw JD: Expression of G proteins in rat cardiac myocytes: effect of KCl depolarization. Am J Physiol 259: H432-H441, 1990

    PubMed  Google Scholar 

  37. Moriartry TM, Padrell E, Carty DJ, Omry G, Landau EM, Iyengar R: Go protein as signal transducer in the pertussis toxin-sensitive phosphatidylinositol pathway. Nature 343: 79–89, 1990

    Article  PubMed  Google Scholar 

  38. Hescheler J, Rosenthal W, Traustwin W, Schultz G: The GTP-binding protein Go regulates neuronal calcium channels. Nature 325: 445–1147, 1987

    PubMed  Google Scholar 

  39. Jiang MT, Moffat MP, Narayanan N: Age-related alterations in the phosphorylation of sarcoplasmic reticulum and myofibrillar proteins and diminished contractile response to isoprenaline in intact rat ventricle. Circ Res 72: 102–111, 1993

    PubMed  Google Scholar 

  40. Brillantes AM, Bezprozvannnaya S, Marks AR: Developmental and tissue-specific regulation of rabbit skeletal and cardiac muscle calcium channels involved in excitation-contraction coupling. Circ Res 75:503–510, 1994

    PubMed  Google Scholar 

  41. Sasse S, Brand NJ, Kyprioanou P, Dhoot GK, Wade R, Arai M, Periasamy, Yacoub MH, Barten PJR: Troponin I gene expression during human cardiac development and in end-stage heart failure. Circ Res 72: 932–938, 1993

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Max-Delbruck-Centrum fur Molekulare Medizin, Forschungsschwerpunkt Kardiologie, Robert-Rossle-Str 10, D-13125, Berlin, Germany

    Sabine Bartel, Peter Karczewski & Ernst-Georg Krause

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  1. Sabine Bartel
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  2. Peter Karczewski
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  3. Ernst-Georg Krause
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Bartel, S., Karczewski, P. & Krause, EG. G proteins, adenylyl cyclase and related phosphoproteins in the developing rat heart. Mol Cell Biochem 163, 31–38 (1996). https://doi.org/10.1007/BF00408638

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