Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Jan;117(1):210–216. doi: 10.1111/j.1476-5381.1996.tb15176.x

Expression of beta 3-adrenoceptor mRNA in rat tissues.

B A Evans 1, M Papaioannou 1, V R Bonazzi 1, R J Summers 1
PMCID: PMC1909365  PMID: 8825365

Abstract

1. This study examines the expression of beta 3-adrenoceptor messenger RNA (beta 3-AR mRNA) in rat tissues to allow comparison with atypical beta-adrenoceptors determined by functional and radioligand binding techniques. 2. A reverse transcription/polymerase chain reaction protocol has been developed for determining the relative amounts of beta 3-AR mRNA in rat tissues. 3. Measurement of adipsin and uncoupling protein (UCP) mRNA was used to examine all tissues for the presence of white and brown adipose tissue which may contribute beta 3-AR mRNA. 4. The beta 3-AR mRNA is expressed at high levels in brown and white adipose tissue, stomach fundus, the longitudinal/circular smooth muscle of both colon and ileum, and colon submucosa. There was substantial expression of adipsin in colon submucosa and moderate expression in fundus, suggesting that in these regions at least some of the beta 3-AR signal may be contributed by fat. Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin. Ileum mucosa and submucosa showed low but readily detectable levels of beta 3-AR. 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver. These results raise the possibility that the atypical beta-AR demonstrated by functional and/or binding studies in muscle and in heart is not the beta 3-AR. 6. By use of two different sets of primers for amplification of beta 3-AR cDNA, no evidence was found for differential splicing of the mRNA in any of the tissues examined. 7. The detection of beta 3-AR mRNA in the gut mucosa and submucosa suggests that in addition to its established roles in lipolysis, thermogenesis and regulation of gut motility beta 3-AR may subserve other functions in the gastrointestinal tract. The absence of beta 3-AR mRNA in rat heart or its presence with adipsin in skeletal muscle suggests that atypical beta-adrenoceptor responses in heart and skeletal muscle are unlikely to be mediated by beta 3-AR.

Full text

PDF
210

Images in this article

213Figure 2
on p.213

Selected References

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

  1. Abe H., Minokoshi Y., Shimazu T. Effect of a beta 3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro. J Endocrinol. 1993 Dec;139(3):479–486. doi: 10.1677/joe.0.1390479. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [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. Arch J. R., Kaumann A. J. Beta 3 and atypical beta-adrenoceptors. Med Res Rev. 1993 Nov;13(6):663–729. doi: 10.1002/med.2610130604. [DOI] [PubMed] [Google Scholar]
  5. Bensaid M., Kaghad M., Rodriguez M., Le Fur G., Caput D. The rat beta 3-adrenergic receptor gene contains an intron. FEBS Lett. 1993 Mar 8;318(3):223–226. doi: 10.1016/0014-5793(93)80516-w. [DOI] [PubMed] [Google Scholar]
  6. Bianchetti A., Manara L. In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical beta-adrenoceptors in rat colon. Br J Pharmacol. 1990 Aug;100(4):831–839. doi: 10.1111/j.1476-5381.1990.tb14100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blin N., Nahmias C., Drumare M. F., Strosberg A. D. Mediation of most atypical effects by species homologues of the beta 3-adrenoceptor. Br J Pharmacol. 1994 Jul;112(3):911–919. doi: 10.1111/j.1476-5381.1994.tb13167.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Blue D. R., Bond R. A., Adham N., Delmendo R., Michel A. D., Eglen R. M., Whiting R. L., Clarke D. E. Antagonist characterization of atypical beta adrenoceptors in guinea pig ileum: blockade by alprenolol and dihydroalprenolol. J Pharmacol Exp Ther. 1990 Mar;252(3):1034–1042. [PubMed] [Google Scholar]
  9. Bond R. A., Clarke D. E. Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the alpha- and beta-subtypes. Br J Pharmacol. 1988 Nov;95(3):723–734. doi: 10.1111/j.1476-5381.1988.tb11698.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bouvier M., Hausdorff W. P., De Blasi A., O'Dowd B. F., Kobilka B. K., Caron M. G., Lefkowitz R. J. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature. 1988 May 26;333(6171):370–373. doi: 10.1038/333370a0. [DOI] [PubMed] [Google Scholar]
  11. Canfield P., Abdul-Ghaffar T. Stimulation of bicarbonate secretion by atypical beta-receptor agonists in rat cecum in vitro. Eur J Pharmacol. 1992 Jun 5;216(2):293–297. doi: 10.1016/0014-2999(92)90373-c. [DOI] [PubMed] [Google Scholar]
  12. Canfield P., Paraskeva P. Beta-adrenoceptor agonist stimulation of acid secretion by rat stomach in vitro is mediated by 'atypical' beta-adrenoceptors. Br J Pharmacol. 1992 Jul;106(3):583–586. doi: 10.1111/j.1476-5381.1992.tb14379.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carpéné C., Galitzky J., Collon P., Esclapez F., Dauzats M., Lafontan M. Desensitization of beta-1 and beta-2, but not beta-3, adrenoceptor-mediated lipolytic responses of adipocytes after long-term norepinephrine infusion. J Pharmacol Exp Ther. 1993 Apr;265(1):237–247. [PubMed] [Google Scholar]
  14. Chaudhry A., Granneman J. G. Influence of cell type upon the desensitization of the beta 3-adrenergic receptor. J Pharmacol Exp Ther. 1994 Dec;271(3):1253–1258. [PubMed] [Google Scholar]
  15. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  16. Cohen M. L., Granneman J. G., Chaudhry A., Schenck K. W., Cushing D. J., Palkowitz A. D. Is the "atypical" beta-receptor in the rat stomach fundus the rat beta 3 receptor? J Pharmacol Exp Ther. 1995 Jan;272(1):446–451. [PubMed] [Google Scholar]
  17. Cook K. S., Min H. Y., Johnson D., Chaplinsky R. J., Flier J. S., Hunt C. R., Spiegelman B. M. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science. 1987 Jul 24;237(4813):402–405. doi: 10.1126/science.3299705. [DOI] [PubMed] [Google Scholar]
  18. Croci T., Cecchi R., Tarantino A., Aureggi G., Bianchetti A., Boigegrain R., Manara L. Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents. Pharmacol Res Commun. 1988 Feb;20(2):147–151. doi: 10.1016/s0031-6989(88)80007-9. [DOI] [PubMed] [Google Scholar]
  19. Emorine L. J., Feve B., Pairault J., Briend-Sutren M. M., Marullo S., Delavier-Klutchko C., Strosberg D. A. Structural basis for functional diversity of beta 1-, beta 2- and beta 3-adrenergic receptors. 1991 Mar 15-Apr 1Biochem Pharmacol. 41(6-7):853–859. doi: 10.1016/0006-2952(91)90188-b. [DOI] [PubMed] [Google Scholar]
  20. Emorine L. J., Marullo S., Briend-Sutren M. M., Patey G., Tate K., Delavier-Klutchko C., Strosberg A. D. Molecular characterization of the human beta 3-adrenergic receptor. Science. 1989 Sep 8;245(4922):1118–1121. doi: 10.1126/science.2570461. [DOI] [PubMed] [Google Scholar]
  21. Granneman J. G. Effects of agonist exposure on the coupling of beta 1 and beta 3 adrenergic receptors to adenylyl cyclase in isolated adipocytes. J Pharmacol Exp Ther. 1992 May;261(2):638–642. [PubMed] [Google Scholar]
  22. Granneman J. G., Lahners K. N. Analysis of human and rodent beta 3-adrenergic receptor messenger ribonucleic acids. Endocrinology. 1994 Sep;135(3):1025–1031. doi: 10.1210/endo.135.3.8070345. [DOI] [PubMed] [Google Scholar]
  23. Granneman J. G., Lahners K. N., Chaudhry A. Characterization of the human beta 3-adrenergic receptor gene. Mol Pharmacol. 1993 Aug;44(2):264–270. [PubMed] [Google Scholar]
  24. Granneman J. G., Lahners K. N., Chaudhry A. Molecular cloning and expression of the rat beta 3-adrenergic receptor. Mol Pharmacol. 1991 Dec;40(6):895–899. [PubMed] [Google Scholar]
  25. Granneman J. G., Lahners K. N., Rao D. D. Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block. Mol Pharmacol. 1992 Dec;42(6):964–970. [PubMed] [Google Scholar]
  26. Growcott J. W., Wilson C., Holloway B., Mainwaring S. Evaluation of ICI D7114, a putative stimulant of brown adipocytes, on histamine-contracted guinea-pig ileum. Br J Pharmacol. 1993 Aug;109(4):1212–1218. doi: 10.1111/j.1476-5381.1993.tb13751.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Hausdorff W. P., Bouvier M., O'Dowd B. F., Irons G. P., Caron M. G., Lefkowitz R. J. Phosphorylation sites on two domains of the beta 2-adrenergic receptor are involved in distinct pathways of receptor desensitization. J Biol Chem. 1989 Jul 25;264(21):12657–12665. [PubMed] [Google Scholar]
  29. Hollenga C., Zaagsma J. Direct evidence for the atypical nature of functional beta-adrenoceptors in rat adipocytes. Br J Pharmacol. 1989 Dec;98(4):1420–1424. doi: 10.1111/j.1476-5381.1989.tb12692.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kaumann A. J. Is there a third heart beta-adrenoceptor? Trends Pharmacol Sci. 1989 Aug;10(8):316–320. doi: 10.1016/0165-6147(89)90065-5. [DOI] [PubMed] [Google Scholar]
  31. Kaumann A. J., Morris T. H., Birnbaumer L. A comparison of the influence of N-isopropyl and N-tert butyl substituents on the affinity of ligands for sinoatrial beta-adrenoceptors in rat atria and beta-adrenoceptors coupled to the adenylyl cyclase in kitten ventricle. Naunyn Schmiedebergs Arch Pharmacol. 1979 May;307(1):1–8. doi: 10.1007/BF00506545. [DOI] [PubMed] [Google Scholar]
  32. Krief S., Lönnqvist F., Raimbault S., Baude B., Van Spronsen A., Arner P., Strosberg A. D., Ricquier D., Emorine L. J. Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest. 1993 Jan;91(1):344–349. doi: 10.1172/JCI116191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kuratani K., Kodama H., Yamaguchi I. Enhancement of gastric mucosal blood flow by beta-3 adrenergic agonists prevents indomethacin-induced antral ulcer in the rat. J Pharmacol Exp Ther. 1994 Aug;270(2):559–565. [PubMed] [Google Scholar]
  34. Liu Y. L., Stock M. J. Acute effects of the beta 3-adrenoceptor agonist, BRL 35135, on tissue glucose utilisation. Br J Pharmacol. 1995 Feb;114(4):888–894. doi: 10.1111/j.1476-5381.1995.tb13287.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. McLaughlin D. P., MacDonald A. Characterization of catecholamine-mediated relaxations in rat isolated gastric fundus: evidence for an atypical beta-adrenoceptor. Br J Pharmacol. 1991 Jun;103(2):1351–1356. doi: 10.1111/j.1476-5381.1991.tb09792.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McLaughlin D. P., MacDonald A. Evidence for the existence of 'atypical' beta-adrenoceptors (beta 3-adrenoceptors) mediating relaxation in the rat distal colon in vitro. Br J Pharmacol. 1990 Nov;101(3):569–574. doi: 10.1111/j.1476-5381.1990.tb14122.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nahmias C., Blin N., Elalouf J. M., Mattei M. G., Strosberg A. D., Emorine L. J. Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes. EMBO J. 1991 Dec;10(12):3721–3727. doi: 10.1002/j.1460-2075.1991.tb04940.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Roberts S. J., Molenaar P., Summers R. J. Characterization of propranolol-resistant (-)-[125I]-cyanopindolol binding sites in rat soleus muscle. Br J Pharmacol. 1993 Jun;109(2):344–352. doi: 10.1111/j.1476-5381.1993.tb13576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. van der Vliet A., Rademaker B., Bast A. A beta adrenoceptor with atypical characteristics is involved in the relaxation of the rat small intestine. J Pharmacol Exp Ther. 1990 Oct;255(1):218–226. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES