Skip to main content
SpringerLink
Log in

Adrenoceptors and the lung: their role in health and disease

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

α- and β-Adrenoceptors have each been divided into two subgroups (α1, α2, β1 and β2). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the α-, but not for the β-subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit. Dysfunctions of adrenoceptormediated effects have been suggested to contribute to some important paediatric disorders such as hyaline membrane syndrome, wet lung, bronchial asthma, cystic fibrosis, and pertussis. Drugs which act on the adrenergic system influence some of these disorders directly. Further studies applying modern techniques to receptor research are needed in order to clarify the basic mechanisms involved in receptor-mediated lung disorders and the activity of drugs in lung tissue.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AC:

adenylate cyclase

ADP:

adenosine diphosphate

β-R:

β-adrenoceptor

cAMP:

cyclic adenosine monophosphate

CF:

cystic fibrosis

GDP:

guanosine diphosphate

GTP:

guanosine triphosphate

IAP:

islet activating protein

References

  1. Ahlquist RP (1948) A study of the adrenotropic receptors. Am J Physiol 153:586–600

    Google Scholar 

  2. Ariens EJ, Simonis AM (1983) Physiological and pharmacological aspects of adrenergic receptor classification. Biochem Pharmacol 32:1539–1545

    Google Scholar 

  3. Backer PF (1986) GTP and calcium release. Nature 320:395

    Google Scholar 

  4. Ballard PL (1986) Hormones and lung maturation. Springer, Berlin Heidelberg New York

    Google Scholar 

  5. Barnes PJ (1984) Adrenergic receptors of normal and asthmatic airways. Eur J Respir Dis [Suppl] 65:72–79

    Google Scholar 

  6. Barnes PJ, Dolbery CT, Macdermot J (1980) Increased pulmonary alpha-adrenergic and reduced β-adrenergic receptors in experimental asthama. Nature 285:569–571

    Google Scholar 

  7. Barnes PJ, Basbaum CB, Nadel JA, Roberts JM (1982) Localization of beta-adrenoceptors in mammalian lung by light microscopic autoradiography. Nature 299:444–447

    Google Scholar 

  8. Barteel TE, Busse WW (1980) Effect of Bordetella pertussis vaccination in mice and the isolated tracheal response to isoprenaline. Allergy 35:291–296

    Google Scholar 

  9. Bergman B, Hedner T, Ludberg P (1980) Pressure-volume relationship and fluid content in fetal rabbit lung after β-receptorstimulating drugs. Pediatr Res 14:1067–1070

    Google Scholar 

  10. Berridge MJ, Irvine RF (1984) Inositol triphosphate, a novel messenger in cellular signal transduction. Nature 312:315–321

    Google Scholar 

  11. Birnbaumer I, Codina J, Mattera R (1985) Structural basis of adenylate cyclase stimulation and inhibition by distinct guanine nucleotide regulatory proteins. In: Cohen P, Houslay MD (eds) Molecular aspects of cellular regulation, vol 4. Molecular mechanisms of transmembrane signalling. Elsevier, Amsterdam, pp 131–182

    Google Scholar 

  12. Boushey HA, Holtzman MJ, Sheller JR, Nadel JA (1980) State of the art. Bronchial hyperreactivity. Am Rev Respir Dis 121:389–413

    Google Scholar 

  13. Brodde OE, Brinkmann M, Schemuth R, O'Hara N, Daul A (1985) Terbutaline-induced desensitization of human lymphocyte β2-adrenoceptors. Accelerated restoration of β-adrenoceptors responsiveness by prednisolone and ketotifen. J Clin Invest 76: 1097–1101

    Google Scholar 

  14. Brodde OE, Kretsch R, Ikezono K, Zerkowski RH, Reidemeister JC (1986) Human β-adrenoceptors: relation of myocardial and lymphocyte β-adrenoceptor density. Science 231:1584–1585

    Google Scholar 

  15. Brooks SM, McGowan K, Altenau P (1979) Relationship between beta-adrenergic binding in lymphocyte and severity of disease in asthma. Chest 75:232–234

    Google Scholar 

  16. Caswell H, Nahorski SR (1983) Beta-adrenoceptor heterogeneity in guinea-pig airways: comparison of functional and receptor labelling studies. Br J Pharmacol 79:965–971

    Google Scholar 

  17. Conolly ME, Grenacre JK (1977) The beta adrenoceptor of the human lymphocyte and human lung parenchyma. Br J Pharmacol 59:17–23

    Google Scholar 

  18. Corbet A, Kolnitt, Perrealut T, Fink J, Rudolph J (1984) Development of sympathetic regulation of phospholipid secretion in fetal rabbit lung. Pediatr Res 18:186A

    Google Scholar 

  19. Cundell D, Danks J, Phillips MJ, Davies RJ (1984) Effect of exercise on isoprenaline-induced lymphocyte cAMP production in atopic asthmatics and atopic and non-atopic non-asthmatic subjects. Clin Allergy 14:433–442

    Google Scholar 

  20. Davies AO, Lefkowitz RT (1984) Regulation of β-adrenergic receptors by steroid hormones. Am Rev Physiol 46:119–129

    Google Scholar 

  21. Davis PB, Hill SC, Ulane MM (1980) Hormone-stimulated cyclic AMP production by skin fibroblasts cultured from healthy persons and patients with cystic fibrosis. Pediatr Res 14:863–868

    Google Scholar 

  22. Davis PB, Dieckman L, Boat IF, Stern RC, Doershuk CF (1983) Beta adrenergic receptors in lymphocytes and granulocytes from patients with cystic fibrosis. J Clin Invest 71:1787–1795

    Google Scholar 

  23. Douglas JS, Ridgway P, Brink C (1977) Airway responses of the guinea-pig in vivo and in vitro. J Pharmacol Exp Ther 202:116–124

    Google Scholar 

  24. Engel G (1981) Subclasses of beta-adrenoceptors — a quantitative estimation of beta 1- and beta 2-adrenoceptors in guinea-pig and human lung. Postgrad Med J 57 [Suppl 1]:77–83

    Google Scholar 

  25. Exton JH (1985) Mechanisms involved in α1-adrenergic responses. In: Lefkowitz RJ, Lindenlaub E (eds) Adrenergic receptors; molucular properties and therapeutic implications. Schattauer, Stuttgart, pp 387–395

    Google Scholar 

  26. Fraser CM, Venter JC (1980) The synthesis of β-adrenergic receptors in cultured human lung cells: induction by glucocorticoids. Biochem Biophys Res Commun 94:390–397

    Google Scholar 

  27. Galant SP, Norton L, Herbst J, Wood C (1981) Impaired beta adrenergic receptor binding and function in cystic fibrosis neutrophils. J Clin Invest 68:253–258

    Google Scholar 

  28. Gilman AG (1983) Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase. J Clin Invest 73:1–4

    Google Scholar 

  29. Gracia-Sainz JA, Boyer JL (1986) Pertussis toxin and the heart. TIPS 7:429–430

    Google Scholar 

  30. Griese M, Reifenhäuser A, Reinhardt D (1987) Impaired β-adrenergic function in lymphocytes of children with pertussis. Pediatr Res 22:240

    Google Scholar 

  31. Griffin JE, Wilson JD (1980) The syndrome of androgen resistance. N Engl J Med 302:198–209

    Google Scholar 

  32. Heuven-Nolsen D van, Folkerts G, Wildt DJ de, Noxkamp FP (1986) The influence of Bordetella pertussis and its constituents on the beta-adrenergic receptor in the guinea pig respiratory system. Life Sci 38:677–685

    Google Scholar 

  33. Hewlett EL (1984) Biological effect of pertussis toxin and Bordella pertussis on adenylate cyclase in intact cells and experimental animals. In: Leive L, Schlessinger D (eds) Microbiology. American Society for Microbiology, Washington, pp 168–171

    Google Scholar 

  34. Hildebrandt JP, Codina J, Risinger R, Birnbaumer L (1984) Identification of a gamma-subunit associated with the adenyl-cyclase regulatory proteins Ns and Ni. J Biol Chem 259:2039–2042

    Google Scholar 

  35. Hirata F, Axelrod J (1980) Phospholipid methylation and biological signal transduction. Science 209:1082–1090

    Google Scholar 

  36. Hirata F, Schiffman E, Venkatasubramanian K, Salomen D, Axelrod J (1980) A phospholiphase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci USA 77:2533–2536

    Google Scholar 

  37. Irestedt K, Lagercrantz H, Hjemdahl P, Hagnevik K, Belfrage P (1982) Fetal and maternal plasma catecholamine levels at elective cesarean section in general or epidural anesthesia versus vaginal delivery. Am J Obstetr Gynecol 142:1004–1010

    Google Scholar 

  38. Jakobs KH, Aktories K, Schultz G (1984) Mechanism of pertussis toxin action on the adenylate cyclase system. Inhibition of the turn on reaction of the inhibitory regulatory site. Eur J Biochem 140:177–181

    Google Scholar 

  39. Kanjanapone V, Hartig-Beecken I, Epstein ME (1980) Effect of isoxsuprine on fetal lung surfactant in rabbits. Pediatr Res 14: 278–281

    Google Scholar 

  40. Katada T, Ui M (1982) Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci USA 79:3129–3133

    Google Scholar 

  41. Kirckpatrick CH, Keller C (1967) Impaired responsiveness to epinephrine in asthma. Am Rev Respir Dis 96:692–699

    Google Scholar 

  42. Kneussl MP, Richardson JB (1978) Alpha-adrenergic receptors in human and canine tracheal and bronchial smooth muscle. J Appl Physiol 45:307–311

    Google Scholar 

  43. Koeter GH, Meurs H, Kauffman HF, Vries K de (1982) The role of the adrenergic system in allergy and bronchial hyperreactivity. Eur J Respir Dis 63 [Suppl 121]:72–78

    Google Scholar 

  44. Körholz D, Seeger K, Griese M, Wahn V, Reinhardt D (1988) Beta-adrenoceptor density and resultion of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children. Eur J Pediatr 147:116–120

    Google Scholar 

  45. Lagercrantz H, Bistolletti P, Nylung L (1981) Sympathoadrenal activity in the foetus during delivery and at birth. In: Stern L, Salle B, Friis-Hansen (eds). Masson, New York, pp 1–12

    Google Scholar 

  46. Lands AM, Arnold A, McAuliff FP (1967) Differentiation of receptor systems activated by sympathomimetic amines. Nature 214:597–598

    Google Scholar 

  47. Larsson K (1985) Studies of sympatho-adrenal reactivity and adrenoceptor function in bronchial asthma. Eur J Respir Dis 66 [Suppl]:1–52

    Google Scholar 

  48. Lefkowitz RJ, Caron MG (1985) Adrenergic receptors: molecular mechanisms of clinically relevant regulation. Clin Res 33:395–406

    Google Scholar 

  49. Lefkowitz RJ, Caron MG (1986) Regulation of adrenergic receptor function by phosphorylation. J Mol Cell Cardiol 18:885–895

    Google Scholar 

  50. Lefkowitz RJ, Stadel JM, Caron MG (1983) Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanism of activation and desensitization. Ann Rev Biochem 52:159–186

    Google Scholar 

  51. Makino S, Ikemori K, Kashima T, Fukuda T (1977) Comparison of cyclic adenosine monophosphate response of lymphocytes in normal and asthmatic subjects to norepinephrine and salbutamol. J Allergy Clin Immunol 59:348–352

    Google Scholar 

  52. Mangos JA, McSherry NR, Benke PJ (1969) Studies on the pathogenesis of cystic fibrosis: the isoproterenol-treated rat as an experimental model: Proceedings of the 5th International Cystic Fibrosis Conference. Cystic Fibrosis Research Trust, Cambridge, pp 25–34

    Google Scholar 

  53. Marino PA, Rooney SA (1981) The effect of labor on surfactant secretion in newborn rabbit slices. Biochim Biophys Acta 664: 389–396

    Google Scholar 

  54. Martinez JR, Adelsstein E, Quissel DO (1975) The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure. Pediatr Res 9:463–469

    Google Scholar 

  55. McPherson MA, Dorn RL, Goodchild RL, Doge JA (1986) Biochemical basis of cystic fibrosis. Nature 323:400

    Google Scholar 

  56. Meurs H, Koeter GH, Vries K de, Kauffman HF (1982) The beta-adrenergic system and allergic bronchial asthma: changes in lymphocyte beta-adrenergic receptor number and adenylate cyclase activity after an allergic-induced asthmatic attack. J Allergy Clin Immunol 70:272–280

    Google Scholar 

  57. Milner AD (1980) Response to bronchodilators in the first five years of life. Eur J Clin Pharmacol 18:117–119

    Google Scholar 

  58. Mita H, Suzuki M, Jasueda H, Shida T (1982) Effect of Brodetella pertussis on alpha- and beta-adrenergic and cholinergic muscarinic receptors in guinea-pig lung membranes. Int Arch Allergy Appl Immunol 69:169–173

    Google Scholar 

  59. Mue S, Shibahara S, Suzuki S, Takahaski M, Hida W, Yamauchi K, Ohmi T, Sasaki T, Takishima T (1980) Bronchial response to metacholine and histamine in monkeys with β-adrenergic blockade. J Allergy Clin Immunol 65:338–345

    Google Scholar 

  60. Nadel JA, Barnes BJ (1984) Autonomic regulation of the airways. Ann Rev Med 35:451–467

    Google Scholar 

  61. Nahorski SR, Barnett DB (1982) Biochemical assessment of adrenoceptor function and regulation: new directions and clinical relevance. Clin Sci 63:97–105

    Google Scholar 

  62. Neijens HJ, Duiverman EJ, Karrebijn KF (1983) Bronchial responsiveness in children. Pediatr Clin North Am 30:829–846

    Google Scholar 

  63. Paterson JW, Ulich KM, Goldie RG (1984) Drug effects on beta-adrenoceptor function in asthma. In: Morley J (ed) Beta-adrenoceptor in asthma. Academic Press, London, pp 245–269

    Google Scholar 

  64. Pavia D, Bateman JRM, Clarke SW (1980) Deposition and clearance of inhaled particles. Clin Resp Physiol 16:335–366

    Google Scholar 

  65. Persson CGA, Ejefält I, Grega GJ, Svensjo E (1982) The role of beta-receptor agonists in the inhibition of pulmonary edema. NY Acad Sci 384:544–556

    Google Scholar 

  66. Plummer AL (1978) The development of drug tolerance to β2-adrenergic agonists. Chest 73:949–957

    Google Scholar 

  67. Quinton M (1983) Chloride impermeability in cystic fibrosis. Nature 301:421–422

    Google Scholar 

  68. Reed CE (1974) Abnormal autonomic mechanisms in asthma. J Allergy Clin Immunol 53:34–41

    Google Scholar 

  69. Reinhardt D, Nagel M, Stemmann EA, Wegner F (1980) Catecholamines and cyclic AMP in allergic and exercise induced asthma of childhood. Eur J Pediatr 134:45–50

    Google Scholar 

  70. Reinhardt D, Becker B, Nagel-Hiemke M, Schiffer T, Zehmisch T (1983) Influence of beta-receptor agonists and glucocorticoids on alpha- and beta-adrenoceptors of isolated blood cells from asthmatic children. Pediatr Pharmacol 3:293–302

    Google Scholar 

  71. Reinhardt D, Zehmisch T, Becker B, Nagel-Hiemke M (1984) Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and non-asthmatic children. Eur J Pediatr 142:111–116

    Google Scholar 

  72. Reinhardt D, Ludwig J, Kusenbach G, Rutschke A (1988) Effects of the antiallergic drug ketotifen on bronchial resistance and β-adrenoceptor density of lymphocytes in children with exercise induced asthma. Dev Pharmacol 11:180–188

    Google Scholar 

  73. Richardson JB (1972) Nerve supply to the lungs. Am Rev Respir dis 119:785–802

    Google Scholar 

  74. Rodbell M (1980) The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284:17–22

    Google Scholar 

  75. Rodger KO (1986) Calcium ions and contraction of airways smooth muscle. In: Kay AB (ed) Asthma. Blackwell, Oxford, pp 116–130

    Google Scholar 

  76. Rooney SA (1985) The surfactant system and lung phospholipid biochemistry. Am Rev Respir Dis 131:439–460

    Google Scholar 

  77. Rugg EL, Barnett DB, Nahorski SR (1978) Coexistence of beta 1- and beta 2-adrenoceptors in mammalian lung: evidence from direct binding studies. Mol Pharmacol 14:996–1005

    Google Scholar 

  78. Sato K, Sato F (1984) Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro. J Clin Invest 73:1763–1771

    Google Scholar 

  79. Scheid CR, Honeyman TW, Fay FS (1979) Mechanism of β-adrenergic relaxation of smooth muscle. Nature 277:32–36

    Google Scholar 

  80. Schultz G, Rosenthal W (1985) Prinzipien der transmembranären Signalumsetzung bei der Wirkung von Hormonen und Neurotransmittern. Arzneim Forsch 35:1879–1885

    Google Scholar 

  81. Schuster A, Elsen A, Kusenbach G, Griese M, Reinhardt D (1988) Studies on the adrenergic system of blood cells from children with cystic fibrosis (CF). Klin Wochenschr (in press)

  82. Spiegel AM, Gierschik P, Levine MA, Downs RW (1985) Clinical implications of guanine nucleotide-binding proteins as receptor-effector couplers. N Engl J Med 312:26–35

    Google Scholar 

  83. Stiles GL, Caron MG, Lefkowitz RJ (1984) β-Adrenergic receptors. Biochemical mechanisms of physiological regulation. Physiol Rev 64:661–743

    Google Scholar 

  84. Szentivanyi A (1968) The beta adrenergic theory of the atopic abnormality in bronchial asthma. J Allergy 42:203–232

    Google Scholar 

  85. Szentivanyi A (1980) The radioligand binding approach in the study of lymphocytic adrenoceptors and the constitutional basic of atopy. J Allergy Clin Immunol 65:5–11

    Google Scholar 

  86. Tal A, Bavilski C, Yohei D, Bearman JE, Gorodisher R, Moses SW (1973) Dexamethasone and salbutamol in the treatment of acute wheezing in infants. Pediatrics 71:13–18

    Google Scholar 

  87. Tashkin DP, Conolly ME, Deutsch RI, Ka Kit HJ, Littner M, Scarpace P, Abrass I (1982) Subsensitization of β-adrenoceptors in airways and lymphocytes of healthy and asthmatic subjects. Am Rev Respir Dis 125:185–193

    Google Scholar 

  88. Tenschert W, Vetter H, Siegenthaler W, Vetter W (1981) Rezeptordysfunktion als pathogenetisches Prinzip bei Hormonresistenz und Stoffwechselerkrankungen. Schweiz Med Wochenschr 111: 174–181

    Google Scholar 

  89. Thies WR, Reinhardt D, Rutschke A, Kusenbach G, Ludwig J (1986) Postnatale Entwicklungen sympatho-adrenerger Systeme bei Früh- und Neugeborenen. Monatsschr Kinderheilkd 134:453–458

    Google Scholar 

  90. Ui M (1984) islet-activating protein, pertussis toxin: a probe for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase. TIPS 5:277–279

    Google Scholar 

  91. Venter JC, Fraser CM (1981) The development of monoclonal antibodies to β-adrenergic receptors and their use in receptor purification and characterization. In: Fellons RR, Eisenbarth GS (eds) Monoclonal antibodies in endocrine research. Raven Press, New York, pp 119–126

    Google Scholar 

  92. Venter JC, Fraser CM, Nelson HS, Middleton E (1983) Adrenergic agents. In: Middleton E, Reed CE, Ellis EF (eds) Allergy. Mosby, St Louis, pp 503–535

    Google Scholar 

  93. Venter JC, Robinson DA, Fraser CM (1984) Beta-adrenergic receptor antibodies, receptor structure and human disease. In: Morley J (ed) Beta-adrenoceptors in asthma. Academic Press, London, pp 147–173

    Google Scholar 

  94. Walters DV, Olver RE (1978) The role of catecholamines in lung liquid absorption at birth. Pediatr Res 12:239–242

    Google Scholar 

  95. Welsh MJ, Liedtke CM (1986) Chlride and potassium channels in cystic fibrosis airway epithelia. Nature 322:467–470

    Google Scholar 

  96. Werner SC, Westarp C von (1983) The thyroid and immunology. Life Sci 32:1–163

    Google Scholar 

  97. Whitsett JA, Darovec-Beckerman C, Pollinger J, Moore J (1982) Ontogeny of β-adrenoceptors in the rat lung: effects of hypothyreoidism. Pediatr Res 15:1363–1369

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Universitäts-Kinderklinik, Moorenstrasse 5, D-4000, Düsseldorf, Federal Republic of Germany

    D. Reinhardt

Authors
  1. D. Reinhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reinhardt, D. Adrenoceptors and the lung: their role in health and disease. Eur J Pediatr 148, 286–293 (1989). https://doi.org/10.1007/BF00444116

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00444116

Key words

Search

Navigation