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. 1989 Dec;98(4):1420–1424. doi: 10.1111/j.1476-5381.1989.tb12692.x

Direct evidence for the atypical nature of functional beta-adrenoceptors in rat adipocytes.

C Hollenga 1, J Zaagsma 1
PMCID: PMC1854821  PMID: 2575416

Abstract

1. The nature of the rat epididymal adipocyte beta-adrenoceptor was investigated by studying the effects of beta 1- and beta 2-selective antagonists on lipolysis induced by (-)-isoprenaline and the lipolytically selective agonist BRL 37344. 2. From 10 nM to 10 microM, the potent and highly selective beta 1-adrenoceptor antagonist CGP 20712A did not influence the concentration-response curve (CRC) of BRL 37344 whereas small but consistent shifts to the right of the (-)-isoprenaline-induced CRC were observed. Clear rightward shifts of the CRCs induced by both (-)-isoprenaline and BRL 37344 were produced only at 100 microM CGP 20712A with the corresponding pA2 values being 4.80 and 4.61, respectively. 3. When the beta 2-selective antagonist ICI 118,551 was used at 10 microM and higher, clear and concentration-dependent shifts to the right of the CRCs of both agonists were observed. The slopes of the Schild plots did not deviate significantly from unity, the pA2 values being 5.49 and 5.33 against (-)-isoprenaline and BRL 37344, respectively. 4. The results demonstrate that (-)-isoprenaline-induced lipolysis in rat white adipocytes is mediated predominantly by atypical beta-adrenoceptors, whereas the typical beta 1-adrenoceptors play a small, subordinate role. The lipolytically selective agonist BRL 37344 acts solely through atypical beta-adrenoceptors.

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Selected References

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

  1. ANTONIS A. SEMIAUTOMATED METHOD FOR THE COLORIMETRIC DETERMINATION OF PLASMA FREE FATTY ACIDS. J Lipid Res. 1965 Apr;6:307–312. [PubMed] [Google Scholar]
  2. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arch J. R., Ainsworth A. T., Cawthorne M. A., Piercy V., Sennitt M. V., Thody V. E., Wilson C., Wilson S. Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature. 1984 May 10;309(5964):163–165. doi: 10.1038/309163a0. [DOI] [PubMed] [Google Scholar]
  4. Bahouth S. W., Malbon C. C. Subclassification of beta-adrenergic receptors of rat fat cells: a re-evaluation. Mol Pharmacol. 1988 Sep;34(3):318–326. [PubMed] [Google Scholar]
  5. Bojanic D., Jansen J. D., Nahorski S. R., Zaagsma J. Atypical characteristics of the beta-adrenoceptor mediating cyclic AMP generation and lipolysis in the rat adipocyte. Br J Pharmacol. 1985 Jan;84(1):131–137. [PMC free article] [PubMed] [Google Scholar]
  6. Bojanic D., Nahorski S. R. Identification and subclassification of rat adipocyte beta-adrenoceptors using (+/-)-[125I]cyanopindolol. Eur J Pharmacol. 1983 Sep 30;93(3-4):235–243. doi: 10.1016/0014-2999(83)90143-7. [DOI] [PubMed] [Google Scholar]
  7. Bojanic D., Nahorski S. R. Irreversible antagonism of beta-adrenoceptors with para-amino-benzyl-carazolol provides further evidence for an atypical rat adipocyte beta-adrenoceptor. J Recept Res. 1984;4(1-6):21–35. doi: 10.3109/10799898409042537. [DOI] [PubMed] [Google Scholar]
  8. Dooley D. J., Bittiger H., Reymann N. C. CGP 20712 A: a useful tool for quantitating beta 1- and beta 2-adrenoceptors. Eur J Pharmacol. 1986 Oct 14;130(1-2):137–139. doi: 10.1016/0014-2999(86)90193-7. [DOI] [PubMed] [Google Scholar]
  9. Harms H. H., Zaagsma J., Van der Wal B. Beta-adrenoceptor studies. III. On the beta-adrenoceptors in rat adipose tissue. Eur J Pharmacol. 1974 Jan;25(1):87–91. doi: 10.1016/0014-2999(74)90098-3. [DOI] [PubMed] [Google Scholar]
  10. Harms H. H., Zaagsma J., de Vente J. Differentiation of beta-adrenoceptors in right atrium, diaphragm and adipose tissue of the rat, using stereoisomers of propranolol, alprenolol, nifenalol and practolol. Life Sci. 1977 Jul 1;21(1):123–128. doi: 10.1016/0024-3205(77)90432-5. [DOI] [PubMed] [Google Scholar]
  11. Honnor R. C., Dhillon G. S., Londos C. cAMP-dependent protein kinase and lipolysis in rat adipocytes. I. Cell preparation, manipulation, and predictability in behavior. J Biol Chem. 1985 Dec 5;260(28):15122–15129. [PubMed] [Google Scholar]
  12. Kaumann A. J. The beta 1-adrenoceptor antagonist CGP 20712 A unmasks beta 2-adrenoceptors activated by (-)-adrenaline in rat sinoatrial node. Naunyn Schmiedebergs Arch Pharmacol. 1986 Apr;332(4):406–409. doi: 10.1007/BF00500096. [DOI] [PubMed] [Google Scholar]
  13. Lands A. M., Arnold A., McAuliff J. P., Luduena F. P., Brown T. G., Jr Differentiation of receptor systems activated by sympathomimetic amines. Nature. 1967 May 6;214(5088):597–598. doi: 10.1038/214597a0. [DOI] [PubMed] [Google Scholar]
  14. MacKay D. How should values of pA2 and affinity constants for pharmacological competitive antagonists be estimated? J Pharm Pharmacol. 1978 May;30(5):312–313. doi: 10.1111/j.2042-7158.1978.tb13237.x. [DOI] [PubMed] [Google Scholar]
  15. RODBELL M. METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS. J Biol Chem. 1964 Feb;239:375–380. [PubMed] [Google Scholar]
  16. de Vente J., Bast A., Van Bree L., Zaagsma J. beta-Adrenoceptor studies. 6. Further investigations on the hybrid nature of the rat adipocyte beta-adrenoceptor. Eur J Pharmacol. 1980 Apr 11;63(1):73–83. doi: 10.1016/0014-2999(80)90118-1. [DOI] [PubMed] [Google Scholar]

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