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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 338, Issue 5, pp 517–522 | Cite as

Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit

  • N. M. Deighton
  • A. D. Brown
  • C. A. Hamilton
  • J. L. Reid
Article

Summary

In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 μmol/kg × h) or ascorbate (0.1 %) for I0 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha2-adrenoceptors were determined.
  1. 1.

    The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h.

     
  2. 2.

    Alpha2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha2-adrenoceptor number and the platelet alpha2-adrenoceptor mediated aggregatory response.

     
  3. 3.

    The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (−)[125I] iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly β1-adrenoceptors) but not in lymphocytes (possessing mainly β2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.

     
  4. 4.

    It is concluded that, in this model, a moderate increase in circulating noradrenaline resulted in substantial decreases in alpha- and beta-adrenoceptor number but in a tissue and/or subtype selective manner.

     

Key words

Noradrenaline infusion Adrenergic receptors Regulation 

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References

  1. Ball N, Danks JL, Dorudi S, Nasmyth PA (1982) Desensitisation by noradrenaline of responses to stimulation of pre- and postsynaptic adrenoceptors. Br J Pharmacol 76:201–210CrossRefGoogle Scholar
  2. Born GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194:927–929CrossRefGoogle Scholar
  3. Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shah P, Jamieson S, Stinson EB (1986) Beta1 and beta2-adrenergic receptor sub-populations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta1-receptor down-regulation in heart failure. Circ Res 59:297–309CrossRefGoogle Scholar
  4. Brodde O-E (1982) Homogenous class of beta1 adrenergic receptors in rat kidney. Identification by (±) [125I] iodocyanopindolol binding. Biochem Pharmacol 31:1743–1747CrossRefGoogle Scholar
  5. Brodde O-E, Kuhlhoff E, Arroyo J, Prywarra A (1983) No evidence for temperature dependent changes in the pharmacological specificity of beta1- and beta2-adrenoceptors in rabbit lung membranes. Naunyn-Schmiedeberg's Arch Pharmacol 322: 20–28CrossRefGoogle Scholar
  6. Brodde O-E, Leifert F-J, Krehl H-J (1981) Coexistence of beta1 and beta2-adrenoceptors in the rabbit heart. Quantitative analysis of the regional distribution by (−)[3H] dihydroalprenolol binding. J Cardiovasc Pharmacol 4:34–43CrossRefGoogle Scholar
  7. Brodde O-E, Schüler S, Kretsch R, Brinkman M, Borst H-G, Hetzer R, Reidelmeister JC, Warnecke H, Zerkowski H-R (1986) Regional distribution of beta-adrenoceptors in the human heart: Coexistence of functional beta1 and beta2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy. J Cardiovasc Pharmacol 8:1235–1242CrossRefGoogle Scholar
  8. Chang HY, Klein RM, Kunos G (1982) Selective desensitisation of cardiac beta adrenoceptors by prolonged in vivo infusion of catecholamines in rats. J Pharmacol Exp Ther 221:784–789PubMedGoogle Scholar
  9. Cheung YD, Barnett DB, Nahorski SR (1986) Heterogeneous properties of alpha2 adrenoceptors in particulate and soluble preparations of human platelet and rat and rabbit kidney. Biochem Pharmacol 35:3767–3775CrossRefGoogle Scholar
  10. Deighton NM, Elfellah MS, Reid JL (1987) Characterisation of beta adrenoceptors in rabbit skeletal muscle and regulation by chronic treatment with adrenaline and noradrenaline (Abstract). Br J Pharmacol 91: 500p Deighton NM; Hamilton CA, Jones CR, Reid JL (1988) The effects of chronic administration of adrenaline on the function and number of adrenoceptors in the rabbit. J Cardiovasc Pharmacol (in press)Google Scholar
  11. Grant JA, Scrutton MC (1980) Interaction of selective alpha-adrenoceptor agonists and antagonists with human and rabbit blood platelets. Br J Pharmacol 71:121–131CrossRefGoogle Scholar
  12. Hamilton CA, Howie CA, Reid JL (1984) Changes in brain alpha adrenoceptors with increasing age in rabbits. Brain Res 322:177–179CrossRefGoogle Scholar
  13. Hamilton CA, Jones CR, Mishra N, Barr S, Reid JL (1985) A comparison of alpha2 adrenoceptor regulation in brain and platelets. Brain Res 347:350–353CrossRefGoogle Scholar
  14. Hamilton CA, Deighton NM, Reid JL (1987) Rapid and reversible desensitisation of vascular and platelet alpha2 adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 335:534–540CrossRefGoogle Scholar
  15. Harden TK (1983) Agonist-induced desensitisation of the beta-adrenergic receptor linked adenylate cyclase. Pharmacol Rev 35:(1), 5–32PubMedGoogle Scholar
  16. Hedberg A, Mattson H (1981) Beta adrenoceptor interaction of full and partial agonists in the cat heart and soleus muscle. J Pharmacol Exp Ther 219:798–808PubMedGoogle Scholar
  17. Jones CR, Hamilton CA, Deighton NM; Reid JL (1985a) Cardiac and lymphocyte beta adrenoceptors in perinephritis hypertension in the rabbit. J Cardiovasc Pharmacol 8:562–566CrossRefGoogle Scholar
  18. Jones CR, Hamilton CA, Whyte KF, Elliott HL, Reid JL (1985b) Acute and chronic regulation of alpha2-adrenoceptor number and function in man. Clin Sci 68 (suppl 10) 129s–132sCrossRefGoogle Scholar
  19. Jones CR, Giembcyz M, Hamilton CA, Rodger IW, Whyte K, Deighton NM, Elliott HL, Reid JL (1986) Desensitisation of platelet alpha2 adrenoceptors following short term infusion of adrenoceptor agonist in man. Clin Sci 70:147 -153CrossRefGoogle Scholar
  20. Landmann RM, Muller SB, Perini C, Wesp M, Buhler FR (1984) Beta adrenergic receptors are different in subpopulations of human circulating lymphocytes. J Recept Res 4:37–50CrossRefGoogle Scholar
  21. Lands AM, Arnold A, McAuliff JP, Luduena FP, Brown TG (1967) Differentiation of receptor systems activated by sympathomimetic amines. Nature 214:597–598CrossRefGoogle Scholar
  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–278Google Scholar
  23. MacGilchrist AJ (1988) Studies on the role of the sympathetic nervous system in cirrhosis of the liver. M.D. Thesis (University of Glasgow, 1988)Google Scholar
  24. Mickey J, Tate R, Lefkowitz RJ (1975) Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (−)-isoproterenol in vitro. J Biol Chem 250 (14):5727–5729PubMedGoogle Scholar
  25. Minneman KP, Pittman RN, Molinoff PB (1981) Beta-adrenergic receptor subtypes: properties, distribution and regulation. Ann Rev Neurosci 4:419–461CrossRefGoogle Scholar
  26. Mukherjee C, Caron M, Lefkowitz RJ (1975) Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta adrenergic receptor binding sites. Proc Natl Acad Sci USA 72 (5):1945–1949CrossRefGoogle Scholar
  27. Peuler JD, Johnson GA (1977) Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci 21:625–636CrossRefGoogle Scholar
  28. Pfeifer MA, Ward K, Molpass T, Stratton J, Hatter J, Evans M, Beiter H, Harker LA, Porte D Jr (1984) Variations in circulating catecholamines fail to alter human platelet alpha2 adrenergic receptor number or affinity for [3H] yohimbine or [3H] dihydroergocryptine. J Clin Invest 74:1063 -1072CrossRefGoogle Scholar
  29. Rugg EL, Barnett DB, Nahorski SR (1978) Coexistence of beta1 and beta2 adrenoceptors in mammalian lung: evidence from direct binding studies. Mol Pharmacol 14:996–1005PubMedGoogle Scholar
  30. Scarpace PJ, Baresi LA, Sanford DA, Abrass IB (1985) Desensitisation and resensitisation of beta-adrenergic receptors in a smooth muscle cell line. Mol Pharmacol 28:495–501PubMedGoogle Scholar
  31. Snaveley MD, Motulsky HJ, O'Conner DT, Ziegler MG, Insel PA (1982) Adrenergic receptors in human and experimental phaeochromocytoma. Clin Exp Hypertens A4 (4 & 5):829–848Google Scholar
  32. Snavely MD, Mahan LC, O'Conner DT, Insel PA (1983) Selective down-regulation of adrenergic receptor subtypes in tissues from rats with phaeochromocytoma. Endocrinol 113:354–360CrossRefGoogle Scholar
  33. Takeyasu K, Higuchi H, Fujita N, Uchida S, Yoshida H (1982) Desensitisation of the alpha adrenergic receptor system in guinea pig vas deferens. Life Sci 31:89–100CrossRefGoogle Scholar
  34. Tsuji K, Tsutsumi S, Ogawa K, Miyazaki Y, Satake T (1987) Cardiac alpha and beta adrenoceptors in rabbits: effects of dietary sodium and cholesterol. Cardiovasc Res 21:39–44CrossRefGoogle Scholar
  35. Tsujimoto G, Hoffman BB (1984) Desensitisation of beta-adrenergic receptor mediated vascular smooth muscle relaxation. Mol Pharmacol 27:210–217Google Scholar
  36. Tsujimoto G, Manger WM, Hoffman BB (1984) Desensitisation of beta adrenergic receptors by phaeochromocytoma. Endocrinol 114:1272–1278CrossRefGoogle Scholar
  37. Valet P, Damase-Michel C, Chamontin B, Durand D, Gaillard G, Salvador M, Montastruc JL (1987) Adrenoceptors in the diagnosis of phaeochromocytoma. Lancet 2 (1):337CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • N. M. Deighton
    • 1
  • A. D. Brown
    • 1
  • C. A. Hamilton
    • 1
  • J. L. Reid
    • 1
  1. 1.University Department of Materia MedicaGlasgowUnited Kingdom

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