Skip to main content
SpringerLink
Log in

Modulation of cell function in the calcium messenger system

  • Chapter
  • First Online:
Reviews of Physiology, Biochemistry and Pharmacology, Volume 95

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 95))

Abstract

A consideration of hormone and neurotransmitter action as an information transfer sequence leads to the conclusion that there are two mechanisms by which the intracellular messengers calcium and cAMP, binding to their respective intracellular receptor proteins, modulate the behavior of specific response elements within the cell. These two mechanisms are those of increasing the amplitude of a particular messenger, and of increasing the sensitivity of activation of a particular response element by a fixed concentration of messenger.

The present discussion of the physiological role of modulation as a critical step in intracellular information transfer leads to the conclusion that there are a large number of discrete cellular processes whose activities are all controlled by the same intracellular messenger via the same intracellular receptor protein, each with its distinctive and variable sensitivity to activation by that intracellular messenger. This means that cellular responses, even those that are high specialized, are not stereotyped but plastic in character, and that this plasticity underlies the organizational elegance of intracellular control.

The characteristics and molecular basis of modulation of cell function by intracellular messengers have been considered. The key molecular feature which underlies modulation is that the messenger receptor proteins possess two types of ligand-binding sites: one for the particular intracellular messenger, and one for a variety of other protein response elements. Binding of ligand to the messenger-binding sites alters protein conformation and thereby ligand-binding at the other site. Likewise, binding of a response element (protein) at the second type of site alters the conformation of the receptor protein and thereby the characteristics of the binding interactions between messenger and receptor protein at the first type of site. It is there intramolecular and intermolecular conversations which constitute the ultimate intracellular dialogue in the flow of information from a change in extracellular messenger concentration to an appropriate cellular response.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adelstein RS, Conti MA, Pato MD (1980) Regulation of myosin light chain kinase by reversible phosphorylation and calcium-calmodulin. Ann NY Acad Sci 356:142–150

    Google Scholar 

  • Ã…kerman KEO, Nicholls DG (1983) Physiological and bioenergetic aspects of mitochondrial calcium transport. Rev Physiol Biochem Pharmacol 95:149–201

    Google Scholar 

  • Ashley CC (1978) Calcium ion regulation in barnacle muscle fibers and its relationship to force development. Ann NY Acad Sci 307:308–329

    Google Scholar 

  • Baker PF (1978) The regulation of intracellular calcium in giant axons of Loligo and Myxicola. Ann NY Acad Sci 307:250–268

    Google Scholar 

  • Becker GL, Fiskum G, Lehninger HL (1980) Regulation of free Ca2+ by liver mitochondria and endoplasmic reticulum. J Biol Chem 255:9009–9012

    Google Scholar 

  • Berridge MJ (1975) The interaction of cyclic nucleotides and calcium in the control of cellular activity. Adv Cyclic Nucleotide Res 6:1–98

    Google Scholar 

  • Berridge MJ (1980) Preliminary measurements of intracellular calcium in an insect salivary gland using a calcium-sensitive microelectrode. Cell Calcium 1:217–228

    Google Scholar 

  • Berridge MJ, Lipke H (1979) Changes in calcium transport across Calliphora salivary glands induced by 5-hydroxytryptamine and cyclic nucleotides. J Exp Biol 78:137–138

    Google Scholar 

  • Blackmore PF, Hughes BP, Shuman EA, Exton JH (1982) α-Adrenergic activation of phosphorylase in liver cells involves mobilization of intracellular calcium without influx of extracellular calcium. J Biol Chem 257:190–197

    Google Scholar 

  • Bloom FE (1979) Cyclic nucleotides in central synaptic function. Fed Proc 38:2203–2207

    Google Scholar 

  • Blumenthal DK, Stull JT (1980) Activation of skeletal muscle myosin light chain kinase by calcium and calmodulin. Biochemistry 19:5608–5614

    Google Scholar 

  • Bolton TB (1979) Mechanism of action of neurotransmitters and other substances on smooth muscle. Physiol Rev 59:609–718

    Google Scholar 

  • Borle AB (1981) Control modulation and regulation of cell calcium. Rev Physiol Biochem Pharmacol 90:13–169

    Google Scholar 

  • Borle A, Uchikawa T (1978) Effects of parathyroid hormone on the distribution and transport of calcium in cultural kidney cells. Endocrinology 102:1725–1732

    Google Scholar 

  • Brinley FJ Jr, Tiffert T, Scarpa A (1978) Mitochondria and other calcium buffers of squid axon studied in situ. J Gen Physiol 72:101–127

    Google Scholar 

  • Brostrom CO, Hunkeler FL, Krebs EG (1971) The regulation of skeletal muscle phosphorylase kinase by Ca2+. J Biol Chem 246:1961–1967

    Google Scholar 

  • Carofoli E, Roman I (1980) Mitochondria and disease. Mol Aspects Med 3:295–429

    Google Scholar 

  • Chapman RA (1979) Excitation-contraction coupling in cardiac muscle. Prog Biophys Mol Biol 35:1–52

    Google Scholar 

  • Cheung WY (1970) Cyclic 3′5′ nucleotide phosphodiesterase. Evidence for and properties of a protein activator. Biochem Biophys Res Commun 38:533–545

    Google Scholar 

  • Cheung WY (1980) Calmodulin plays a pivotal role in cellular regulation. Science 207:19–27

    Google Scholar 

  • Cheung WY, Lynch TJ, Wallace RW, Tallant EC (1981) cAMP renders Ca2+-dependent phosphodiesterase refractory to inhibition by a calmodulin-binding protein (calcineuria). J Biol Chem 256:4439–4443

    Google Scholar 

  • Clayberger C, Goodman DBP, Rasmussen H (1981) Regulation of cAMP metabolism in the rat erythrocyte during chronic adrenergic stimulation. Evidence for calmodulin-mediated alteration of membrane bound phosphodiesterase activity. J Membr Biol 58:191–201

    Google Scholar 

  • Cohen P (1979) The hormonal control of glycogen metabolism in mammalian muscle by multivalent phosphorylation. Biochem Soc Trans 7:459–480

    Google Scholar 

  • Conti MA, Adelstein RS (1980) Phosphorylation of cyclic adenosine 3′:5′-monophosphate-dependent protein kinase regulates myosin light chain kinase. Fed Proc 39:1569–1573

    Google Scholar 

  • Crouch TH, Klee CB (1980) Positive cooperative binding of calcium to bovine brain calmodulin. Biochemistry 19:3692–3698

    Google Scholar 

  • DeLorenzo RJ (1981) The calmodulin hypothesis of neurotransmission. Cell Calcium 2:365–385

    Google Scholar 

  • DePaoli-Roach AA, Roach PJ, Larner J (1979) Rabbit skeletal muscle phosphorylase kinase. J Biol Chem 254:4212–4219

    Google Scholar 

  • Dipolo R, Requena J, Brinley FJ Jr, Mullins LJ, Scarpa A, Tiffert T (1976) Ionized calcium concentrations in squid axons. J Gen Physiol 67:433–467

    Google Scholar 

  • Ebashi S (1963) Third component participating in the superprecipitation of ‘Natural Aclomyosin'. Nature 200:1010

    Google Scholar 

  • Ebashi S (1976) Excitation-contraction coupling. Annu Rev Physiol 38:293–313

    Google Scholar 

  • Ebashi S, Endo M, Ohtsuki I (1969) Control of muscle contraction. Q Rev Biophys 2:351–384

    Google Scholar 

  • Ebashi S, Mikawa T, Hirata M, Nonomura Y (1978) The regulatory role of calcium in muscle. Ann NY Acad Sci 307:451–461

    Google Scholar 

  • Eldik LJ, Piperno G, Watterson DM (1980) Comparative biochemistry of calmodulins and calmodulin-like proteins. Ann NY Acad Sci 356:36–41

    Google Scholar 

  • England PJ (1975) Correlation between contraction and phosphorylation of the inhibitory subunit of troponin in perfused rat heart. FEBS Lett 50:57–60

    Google Scholar 

  • Fabiato A (1981) Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol 78:457–497

    Google Scholar 

  • Fleckenstein A (1974) Drug-induced changes in cardiac energy. Adv Cardiol 12:183–197

    Google Scholar 

  • Foreman JC, Mongar JR, Compertz BP (1973) Calcium ionophores and movement of calcium ions following the physiological stimulus to a secretory response. Nature 245:249–251

    Google Scholar 

  • Goodman M, Pechere J-F, Haiech J, Demaille JG (1979) Evolutionary diversification of structure and function in the family of intracellular calcium binding proteins. J Mol Evol 13:331–352

    Google Scholar 

  • Grand RJ, Perry ASV, Weeks RA (1979) Troponin C-like proteins (calmodulin) from mammalian smooth muscle and other tissues. Biochem J 177:521–529

    Google Scholar 

  • Greengard P (1978) Cyclic nucleotides, phosphorylated proteins, and neuronal function. Raven Press, New York

    Google Scholar 

  • Haiech J, Klee CB, Vemaille JG (1981) Effects of cations on affinity of calmodulin for calcium: ordered bindings of calcium ions allows the specific activation of calmodulin-stimulated enzymes. Biochemistry 20:3890–3897

    Google Scholar 

  • Hanbauer I, Pradham S, Yang HTY (1980) Role of calmodulin in dopaminergic transmission. Ann NY Acad Sci 356:292–303

    Google Scholar 

  • Hansford RG, Chappell JB (1967) The effect of Ca2+ on the oxidation of glycerophosphate by blowfly flight muscle mitochondria. Biochem Biophys Res Commun 27:686–692

    Google Scholar 

  • Hartshorne DJ, Persechini AJ (1980) Phosphorylation of myosin as a regulatory component in smooth muscle. Ann NY Acad Sci 356:130–141

    Google Scholar 

  • Huang CY, Chau V, Chock PB, Wang JH, Sharma RK (1981) Mechanisms of activation of cyclic nucleotide phosphodiesterase: requirement of the binding of four Ca2+ to calmodulin for activation. Proc Natl Acad Sci USA 78:871–874

    Google Scholar 

  • Huttner W, Greengard P (1979) Multiple phosphorylation sites in protein I and their differential regulation by cyclic AMP and calcium. Proc Natl Acad Sci USA 76:5402–5406

    Google Scholar 

  • Jamieson GA, Bronson DD, Schachat FH, Vanaman TC (1980) Structure and function relationships among calmodulins and troponin C-like proteins from divergent eukaryotic organisms. Ann NY Acad Sci 356:1–13

    Google Scholar 

  • Kakiuchi S, Yamazaki R (1980) Calcium dependent phosphodiesterase activity and its activating factor (PAF) from brain. Biochem Biophys Res Commun 41:1104–1110

    Google Scholar 

  • Katz B (1966) Nerve, muscle and synapse. McGraw-Hill, New York

    Google Scholar 

  • Kebabian JW (1977) Biochemical regulation and physiological significance of cyclic nucleotides in the nervous system. Adv Cyclic Nucleotide Res 8:421–508

    Google Scholar 

  • Keller CH, LaPorte DC, Toscano WA Jr, Storm DR, Westcott KR (1980) Ca2+ regulation of cyclic nucleotide metabolism. Ann NY Acad Sci 356:205–219

    Google Scholar 

  • Kerrick WGL, Hoar PE, Cassidy PA (1980) Calcium-activated tension: the role of myosin light chain phosphorylation. Fed Proc 39:1558–1563

    Google Scholar 

  • Kirchberger MA, Tada M (1976) Effects of adenosine 3′:5′-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting muscles. J Biol Chem 251:725–729

    Google Scholar 

  • Klee CB (1977) Conformational transition accompanying the binding of Ca2+ to the protein activator of 3′,5′-cyclic adenosine monophosphate phosphodiesterase. Biochemistry 16:1017–1024

    Google Scholar 

  • Kretsinger RH (1975) Hypothesis: calcium modulated proteins contain EF-bands. In: Carofoli E, Clementi F, Drabikowski W, Margreth A (eds) Calcium transport in contraction and secretion. North Holland, Amsterdam, pp 469–478

    Google Scholar 

  • Kretsinger RH (1980) Crystallographic studies of calmodulin and homologs, Ann NY Acad Sci 356:14–19

    Google Scholar 

  • LePeuch CH, Haiech J, Demaille JG (1979) Concerted regulation of cardiac sarcoplasmic reticulum calcium transport by cyclic adenosine monophosphate dependent and calcium-calmodulin-dependent phosphorylation. Biochemistry 18:5150–5157

    Google Scholar 

  • Means AR, Dedman JR (1980) Calmodulin — an intracellular calcium receptor. Nature 285:73–77

    Google Scholar 

  • Murphy E, Catt K, Rich TL, Williamson JR (1980) Hormonal effects on calcium homeostasis in isolated hepatocytes. J Biol Chem 255:6600–6608

    Google Scholar 

  • Nicholls DG (1978) The regulation of extramitochondrial free calcium ion concentration by rat liver mitochondria. Biochem J 179:511–522

    Google Scholar 

  • O'Doherty J, Youmans SJ, Armstrong WMcD, Stark RJ (1980) Calcium regulation during stimulus secretion coupling: continuous measurement of intracellular calcium activities. Science 209:510–513

    Google Scholar 

  • Pearson GT, Singh J, Daoud MS, Davison JS, Petersen OH (1981) Control of pancreatic cyclic nucleotide levels and amylase secretion by noncholinergic, nonadrenergic nerves. J Biol Chem 256:11025–11031

    Google Scholar 

  • Penniston JT, Graf E, Itano T (1980) Calmodulin regulation of the Ca2+ pump of erythrocyte membranes. Ann NY Acad Sci 356:245–257

    Google Scholar 

  • Perry SV, Amphlett GA, Grand RJA, Jackson P, Syska H, Wilkinson JM (1975) Some aspects of the primary structure and the function of the components of the troponin complex. In: Carofoli E, Clementi F, Drabikowski W, Margreth A (eds) Calcium transport in secretion and contraction. North Holland, Amsterdam, pp 431–440

    Google Scholar 

  • Rasmussen H (1980) Cell communication, calcium ion and cyclic adenosine monophosphate. Science 170:404–412

    Google Scholar 

  • Rasmussen H (1980) Calcium and cAMP in stimulus-response coupling. Ann NY Acad Sci 356:346–353

    Google Scholar 

  • Rasmussen H (1981) Calcium and cAMP as synarchic messengers. Wiley and Sons, New York

    Google Scholar 

  • Rasmussen H, Bikle DD (1975) Calcium and non-vesicular secretion in the kidney: calcium and mitochondrial functions. In: Carofoli E, Clementi F, Drabikowski W, Margreth A (eds) Calcium transport in contraction and secretion. North Holland, Amsterdam, pp 111–122

    Google Scholar 

  • Rasmussen H, Goodman DBG (1977) Relationship between calcium and cyclic nucleotides in cell activation. Physiol Rev 57:422–509

    Google Scholar 

  • Rasmussen H, Waisman DM (1981) The messenger function of calcium in endocrine systems. Biochem Act Horm VIII:1–115

    Google Scholar 

  • Ray KP, England PJ (1976) Phosphorylation of the inhibitory subunit of troponin and its effect on the calcium dependence of cardiac myofibril adenosine triphosphatase. FEBS Lett 70:11–16

    Google Scholar 

  • Reuter H, Scholz H (1976) A study of the ion selectivity and the kinetic properties of the calcium dependent slow inward current in mammalian cardiac muscle. J Physiol (Lond) 264:17–47

    Google Scholar 

  • Robison GA, Butcher RW, Sutherland EW (1971) Cyclic AMP. Academic Press, New York

    Google Scholar 

  • Scarpa A, Brinley FJ, Tiffert T, Dubyak GR (1978) Metallochromic indicators of ionized calcium. Ann NY Acad Sci 307:86–111

    Google Scholar 

  • Schanne FAX, Kane AB, Young EE, Farber JL (1979) Calcium-dependence of toxic cell death: a final common pathway. Science 206:206–208

    Google Scholar 

  • Scharff P (1981) Calmodulin and its role in cellular activation. Cell Calcium 2:1–28

    Google Scholar 

  • Schulz I (1980) Messenger role of calcium in function of pancreatic acinar cell. Am J Physiol 239:6335–6347

    Google Scholar 

  • Shenolikar S, Cohen PTW, Cohen P, Nairn AC, Perry SV (1979) The role of calmodulin in the structure and regulation of phosphorylase kinase from rabbit skeletal muscle. Eur J Biochem 100:329–327

    Google Scholar 

  • Silver PJ, Holroyde MJ, Solaro J, Disalvo J (1981) Ca2+, calmodulin and cyclic AMP-dependent modulation of actin-myosin interactions in aorta. Biochim Biophys Acta 674:65–70

    Google Scholar 

  • Smith SB, White HD, Siegel JB, Krebs EG (1981) Cyclic AMP-dependent protein kinase I: cyclic nucleotide binding, structural changes, and release of catalytic subunits. Proc Natl Acad Sci USA 78:1591–1595

    Google Scholar 

  • Sutherland EW, Rall EW (1958) Formation of cyclic adenine ribonucleotide by tissue particles. J Biol Chem 232:1065–1076

    Google Scholar 

  • Teo TS, Wang JH (1973) Mechanism of activation of a cyclic adenosine 3′:5′-monophosphate phosphodiesterase from bovine heart by calcium ions — identification of the protein activator as a Ca2+ binding protein. J Biol Chem 248:5950–5955

    Google Scholar 

  • Tsien RW (1977) Cyclic AMP and contractile activity in heart. Adv Cyclic Nucleotide Res 8:363–411

    Google Scholar 

  • Vincenzi FF, Hinds TR, Raess BV (1980) Calmodulin and the plasma membrane calcium pump. Ann NY Acad Sci 256:233–244

    Google Scholar 

  • Waisman DM, Singh TJ, Wang JH (1978) The modulator-dependent protein kinase. J Biol Chem 253:3387–3390

    Google Scholar 

  • Waisman DM, Gimble J, Goodman DBP, Rasmussen H (1981) Studies of the Ca2+ transport mechanism of human inside-out plasma membrane vesicles. I. Regulation of the Ca2+ pump by calmodulin. J Biol Chem 256:409–414

    Google Scholar 

  • Walkenbach RJ, Hazen R, Larner J (1978) Reversible inhibition of cyclic AMP-dependent protein kinase by insulin. Mol Cell Biochem 19:31–41

    Google Scholar 

  • Walsh KX, Millikin DM, Schendler KK, Reimann EM (1980) Stimulation of phosphorylase b kinase by the calcium-dependent regulator. J Biol Chem 255:5036–5042

    Google Scholar 

  • Wang JH, Waisman DM (1979) Calmodulin and its role in the second messenger system. Curr Top Cell Regul 15:47–107

    Google Scholar 

  • Wang JH, Teo TS, Ho HC, Stevens FC (1975) Bovine heart protein activator of cyclic nucleotide phosphodiesterase. Adv Cyclic Nucleotide Res 5:179–194

    Google Scholar 

  • Wang JH, Sharma RK, Huan CY, Chau V, Chock PB (1980) On the mechanism of activation of cyclic nucleotide phosphodiesterase by calmodulin. Ann NY Acad Sci 356:190–204

    Google Scholar 

  • Wrogemann K, Pena SDJ (1976) Mitochondrial calcium overload: a general mechanism for cell necrosis in muscle disease. Lancet I:672–673

    Google Scholar 

  • Wyborny LE, Reddy YS (1978) Phosphorylated cardiac myofibrils and their effect on ATPase activity. Biochem Biophys Res Commun 81:1175–1179

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Internal Medicine, Physiology and Cell Biology, Yale University School of Medicine, 06510, New Haven, CT, USA

    David M. Waisman

Authors
  1. Howard Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Waisman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer-Verlag

About this chapter

Cite this chapter

Rasmussen, H., Waisman, D.M. (1983). Modulation of cell function in the calcium messenger system. In: Reviews of Physiology, Biochemistry and Pharmacology, Volume 95. Reviews of Physiology, Biochemistry and Pharmacology, vol 95. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0034098

Download citation

  • DOI: https://doi.org/10.1007/BFb0034098

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-11736-0

  • Online ISBN: 978-3-540-39476-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation