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. 1987 Dec;92(4):827–834. doi: 10.1111/j.1476-5381.1987.tb11387.x

Independent regulation of beta 1- and beta 2-adrenoceptors.

M Beer 1, S Hacker 1, J Poat 1, S M Stahl 1
PMCID: PMC1853710  PMID: 2892556

Abstract

1 The down-regulation of beta-adrenoceptors has been postulated as a biochemical marker of antidepressant efficacy. Here we demonstrate that chronic treatment with desipramine down-regulates beta 1-adrenoceptors in rat cerebral cortex and that beta-adrenoceptor subtypes can be independently regulated by treatment with different beta-adrenoceptor agonists. 2 Desipramine, (+/-)-clenbuterol, prenalterol, corwin (20 mg kg-1 daily) and corwin (10 mg kg-1 daily) were administered to male, Sprague-Dawley rats, over eight days, by means of osmotic Alzet pumps placed subcutaneously and removed 24 h before analysis. Control rats received vehicle only. The beta 1- and beta 2-adrenoceptor populations were measured in cerebral cortex by a modified (-)-[125I]-pindolol receptor binding assay. 3 The conventional antidepressant, desipramine, preferentially down-regulated beta 1-adrenoceptors whereas the non-selective beta-adrenoceptor agonist (+/-)-clenbuterol preferentially down-regulated beta 2-adrenoceptors. The beta 1-selective partial agonist, prenalterol, up-regulated beta 1-adrenoceptors perhaps acting more as an antagonist than as an agonist. Finally, neither dose of corwin had any significant effect on beta-adrenoceptor number.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banerjee S. P., Kung L. S., Riggi S. J., Chanda S. K. Development of beta-adrenergic receptor subsensitivity by antidepressants. Nature. 1977 Aug 4;268(5619):455–456. doi: 10.1038/268455a0. [DOI] [PubMed] [Google Scholar]
  2. Bergstrom D. A., Kellar K. J. Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. J Pharmacol Exp Ther. 1979 May;209(2):256–261. [PubMed] [Google Scholar]
  3. Bergstrom D. A., Kellar K. J. Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature. 1979 Mar 29;278(5703):464–466. doi: 10.1038/278464a0. [DOI] [PubMed] [Google Scholar]
  4. Carlsson E., Dahlöf C. G., Hedberg A., Persson H., Tångstrand B. Differentiation of cardiac chronotropic and inotropic effects of beta-adrenoceptor agonists. Naunyn Schmiedebergs Arch Pharmacol. 1977 Nov;300(2):101–105. doi: 10.1007/BF00505039. [DOI] [PubMed] [Google Scholar]
  5. Cohen M. L., Wiley K. S., Bemis K. G. Analysis of the beta 1 and beta 2 adrenoceptor interactions of the partial agonist, clenbuterol (NAB365), in the rat jugular vein and atria. Naunyn Schmiedebergs Arch Pharmacol. 1982 Aug;320(2):145–151. doi: 10.1007/BF00506314. [DOI] [PubMed] [Google Scholar]
  6. Dooley D. J., Hauser K. L. Subchronic infusion of clenbuterol, a beta-adrenergic agonist, decreases the cerebellar beta receptor. Neurosci Lett. 1983 Mar 28;36(1):93–97. doi: 10.1016/0304-3940(83)90492-5. [DOI] [PubMed] [Google Scholar]
  7. Doyle V. M., Bühler F. R., Bürgisser E. Inappropriate correction for radioactive decay in fully iodinated adrenergic radioligands. Eur J Pharmacol. 1984 Apr 6;99(4):353–356. doi: 10.1016/0014-2999(84)90146-8. [DOI] [PubMed] [Google Scholar]
  8. Frazer A., Ordway G., O'Donnell J., Vos P., Wolfe B. Effect of repeated administration of clenbuterol on the regulation of beta-adrenoceptors in the central nervous system of the rat. Ciba Found Symp. 1986;123:170–190. doi: 10.1002/9780470513361.ch10. [DOI] [PubMed] [Google Scholar]
  9. Hall H., Sällemark M., Ross S. B. Clenbuterol, a central beta-adrenoceptor agonist. Acta Pharmacol Toxicol (Copenh) 1980 Aug;47(2):159–160. doi: 10.1111/j.1600-0773.1980.tb01857.x. [DOI] [PubMed] [Google Scholar]
  10. Hancock A. A., Marsh C. L. Agonist interactions with beta-adrenergic receptors following chronic administration of desipramine or the atypical antidepressants, iprindole and mianserin. J Recept Res. 1985;5(5-6):311–334. doi: 10.3109/10799898509041885. [DOI] [PubMed] [Google Scholar]
  11. Hirata F., Axelrod J. Enzymatic methylation of phosphatidylethanolamine increases erythrocyte membrane fluidity. Nature. 1978 Sep 21;275(5677):219–220. doi: 10.1038/275219a0. [DOI] [PubMed] [Google Scholar]
  12. Honegger U. E., Disler B., Wiesmann U. N. Chronic exposure of human cells in culture to the tricyclic antidepressant desipramine reduces the number of beta-adrenoceptors. Biochem Pharmacol. 1986 Jun 1;35(11):1899–1902. doi: 10.1016/0006-2952(86)90309-6. [DOI] [PubMed] [Google Scholar]
  13. Kitada Y., Miyauchi T., Kosasa T., Satoh S. The significance of beta-adrenoceptor down regulation in the desipramine action in the forced swimming test. Naunyn Schmiedebergs Arch Pharmacol. 1986 May;333(1):31–35. doi: 10.1007/BF00569656. [DOI] [PubMed] [Google Scholar]
  14. Lecrubier Y., Puech A. J., Jouvent R., Simon P., Widlocher D. A beta adrenergic stimulant (salbutamol) versus clomipramine in depression: a controlled study. Br J Psychiatry. 1980 Apr;136:354–358. doi: 10.1192/bjp.136.4.354. [DOI] [PubMed] [Google Scholar]
  15. McGonigle P., Neve K. A., Molinoff P. B. A quantitative method of analyzing the interaction of slightly selective radioligands with multiple receptor subtypes. Mol Pharmacol. 1986 Oct;30(4):329–337. [PubMed] [Google Scholar]
  16. Minneman K. P., Dibner M. D., Wolfe B. B., Molinoff P. B. beta1- and beta2-Adrenergic receptors in rat cerebral cortex are independently regulated. Science. 1979 May 25;204(4395):866–868. doi: 10.1126/science.35829. [DOI] [PubMed] [Google Scholar]
  17. Minneman K. P., Hegstrand L. R., Molinoff P. B. Simultaneous determination of beta-1 and beta-2-adrenergic receptors in tissues containing both receptor subtypes. Mol Pharmacol. 1979 Jul;16(1):34–46. [PubMed] [Google Scholar]
  18. Mishra R., Janowsky A., Sulser F. Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain: subsensitivity without reduction in beta-adrenergic receptor binding. Neuropharmacology. 1980 Oct;19(10):983–987. doi: 10.1016/0028-3908(80)90009-x. [DOI] [PubMed] [Google Scholar]
  19. Motulsky H. J., Insel P. A. Adrenergic receptors in man: direct identification, physiologic regulation, and clinical alterations. N Engl J Med. 1982 Jul 1;307(1):18–29. doi: 10.1056/NEJM198207013070104. [DOI] [PubMed] [Google Scholar]
  20. Nerme V., Severne Y., Abrahamsson T., Vauquelin G. Endogenous noradrenaline masks beta-adrenergic receptors in rat heart membranes via tight agonist binding. Biochem Pharmacol. 1985 Aug 15;34(16):2917–2922. doi: 10.1016/0006-2952(85)90016-4. [DOI] [PubMed] [Google Scholar]
  21. Nimgaonkar V. L., Goodwin G. M., Davies C. L., Green A. R. Down-regulation of beta-adrenoceptors in rat cortex by repeated administration of desipramine, electroconvulsive shock and clenbuterol requires 5-HT neurones but not 5-HT. Neuropharmacology. 1985 Apr;24(4):279–283. doi: 10.1016/0028-3908(85)90132-7. [DOI] [PubMed] [Google Scholar]
  22. O'Donnell J. M., Frazer A. Effects of clenbuterol and antidepressant drugs on beta adrenergic receptor/N-protein coupling in the cerebral cortex of the rat. J Pharmacol Exp Ther. 1985 Jul;234(1):30–36. [PubMed] [Google Scholar]
  23. Okada F., Tokumitsu Y., Ui M. Desensitization of beta-adrenergic receptor-coupled adenylate cyclase in cerebral cortex after in vivo treatment of rats with desipramine. J Neurochem. 1986 Aug;47(2):454–459. doi: 10.1111/j.1471-4159.1986.tb04522.x. [DOI] [PubMed] [Google Scholar]
  24. Peroutka S. J., Snyder S. H. Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science. 1980 Oct 3;210(4465):88–90. doi: 10.1126/science.6251550. [DOI] [PubMed] [Google Scholar]
  25. Rainbow T. C., Parsons B., Wolfe B. B. Quantitative autoradiography of beta 1- and beta 2-adrenergic receptors in rat brain. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1585–1589. doi: 10.1073/pnas.81.5.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ross S. B. Antagonism of reserpine-induced hypothermia in mice by some beta-adrenoceptor agonists. Acta Pharmacol Toxicol (Copenh) 1980 Nov;47(5):347–350. doi: 10.1111/j.1600-0773.1980.tb01570.x. [DOI] [PubMed] [Google Scholar]
  27. Sellinger-Barnette M. M., Mendels J., Frazer A. The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain. Neuropharmacology. 1980 May;19(5):447–454. doi: 10.1016/0028-3908(80)90052-0. [DOI] [PubMed] [Google Scholar]
  28. Stadel J. M., Nambi P., Shorr R. G., Sawyer D. F., Caron M. G., Lefkowitz R. J. Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3173–3177. doi: 10.1073/pnas.80.11.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stiles G. L., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev. 1984 Apr;64(2):661–743. doi: 10.1152/physrev.1984.64.2.661. [DOI] [PubMed] [Google Scholar]
  30. Sugrue M. F. Do antidepressants possess a common mechanism of action? Biochem Pharmacol. 1983 Jun 15;32(12):1811–1817. doi: 10.1016/0006-2952(83)90043-6. [DOI] [PubMed] [Google Scholar]
  31. Sulser F., Vetulani J., Mobley P. L. Mode of action of antidepressant drugs. Biochem Pharmacol. 1978 Feb 1;27(3):257–261. doi: 10.1016/0006-2952(78)90226-5. [DOI] [PubMed] [Google Scholar]
  32. Suranyi-Cadotte B. E., Dam T. V., Bodnoff S., Quirion R. Variability of chronic antidepressant treatments on beta-adrenergic receptor sites. Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(5-6):765–768. doi: 10.1016/0278-5846(85)90057-0. [DOI] [PubMed] [Google Scholar]
  33. Takamura T., Nagai S., Sugiyama S., Ozawa T. Mechanism responsible for "down regulation" during successive beta-agonist administration in rat hearts. Jpn Circ J. 1985 Dec;49(12):1243–1251. doi: 10.1253/jcj.49.1243. [DOI] [PubMed] [Google Scholar]
  34. Waldeck B., Widmark E. Steric aspects of agonism and antagonism at beta-adrenoceptors: experiments with the enantiomers of clenbuterol. Acta Pharmacol Toxicol (Copenh) 1985 Mar;56(3):221–227. doi: 10.1111/j.1600-0773.1985.tb01279.x. [DOI] [PubMed] [Google Scholar]
  35. Widlöcher D., Lecrubier Y., Jouvent R., Puech A. J., Simon P. Antidepressant effect of salbutamol. Lancet. 1977 Oct 8;2(8041):767–768. doi: 10.1016/s0140-6736(77)90279-3. [DOI] [PubMed] [Google Scholar]
  36. Wolfe B. B., Minneman K. P., Molinoff P. B. Selective increases in the density of cerebellar beta-1-adrenergic receptors. Brain Res. 1982 Feb 25;234(2):474–479. doi: 10.1016/0006-8993(82)90890-3. [DOI] [PubMed] [Google Scholar]

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