Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 May;97(1):229–239. doi: 10.1111/j.1476-5381.1989.tb11946.x

Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects.

P Valet 1, M Taouis 1, M A Tran 1, P Montastruc 1, M Lafontan 1, M Berlan 1
PMCID: PMC1854488  PMID: 2566353

Abstract

1. Lipid mobilization during a hypocaloric diet may be enhanced by a pharmacological approach using beta 2-adrenoceptor agonists or alpha 2-adrenoceptor antagonists. Studies were undertaken in the dog, an animal model presenting fat cell antilipolytic alpha 2- and lipolytic beta-adrenoceptors, in order, firstly, to demonstrate the presence of beta 2 subtype adrenoceptors on adipocytes and, secondly, to compare the effects of procaterol (beta 2-adrenoceptor agonist) and of yohimbine (alpha 2-adrenoceptor antagonist) on metabolic, endocrinological and cardiovascular parameters. 2. Procaterol strongly stimulates lipolysis in dog adipocytes in vitro. The utilisation of selective beta 1- and beta 2-adrenoceptor antagonists (bisoprolol and ICI 118,551) in both lipolysis and binding studies (displacement of [3H]-dihydroalprenolol binding) demonstrated the presence of the two beta-adrenoceptor subtypes in dog fat cells. 3. Infusion of either yohimbine or procaterol (10 and 0.4 nmol min-1 kg-1, respectively for 30 min), provoked an equivalent increase in plasma non-esterified fatty acids (+100%). Procaterol, but not yohimbine, induced hyperglycaemia (+120%). Plasma insulin was weakly enhanced by yohimbine (+120%) as compared to the increase given by procaterol (+500%). 4. Both drugs stimulated sympathetic nervous system activity, as indicated by the increased plasma noradrenaline concentration, but only yohimbine increased the plasma adrenaline level. 5. Cardiovascular measurements indicated that procaterol strongly enhances heart rate and transiently decreases mean blood pressure. Yohimbine exhibits a weaker effect on heart rate and slightly increases mean blood pressure. 6. The present work clearly indicates that lipid mobilization is enhanced during fasting in the dog by selective beta 2-adrenoceptor stimulation or by alpha 2-adrenoceptor blockade. This enhanced lipolytic effect may result either from a direct action of the drugs on the adrenoceptors of fat cells or from an activation of the sympathetic nervous system. Procaterol suffers major limitations since it strongly increases heart rate, immunoreactive insulin and glycaemia. On the other hand, yohimbine induces only minor modifications both in cardiovascular and endocrinological parameters.

Full text

PDF
230

Selected References

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

  1. Arner P., Engfeldt P., Nowak J. In vivo observations on the lipolytic effect of noradrenaline during therapeutic fasting. J Clin Endocrinol Metab. 1981 Dec;53(6):1207–1212. doi: 10.1210/jcem-53-6-1207. [DOI] [PubMed] [Google Scholar]
  2. Arner P., Ostman J. Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding. Acta Med Scand. 1976;200(4):273–279. [PubMed] [Google Scholar]
  3. Arnold J. M., O'Connor P. C., Riddell J. G., Harron D. W., Shanks R. G., McDevitt D. G. Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man. Br J Clin Pharmacol. 1985 May;19(5):619–630. doi: 10.1111/j.1365-2125.1985.tb02689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berlan M., Carpene C., Lafontan M., Dang-Tran L. Alpha-2 adrenergic antilipolytic effect in dog fat cells: incidence of obesity and adipose tissue localization. Horm Metab Res. 1982 May;14(5):257–260. doi: 10.1055/s-2007-1018986. [DOI] [PubMed] [Google Scholar]
  5. Berlan M., Lafontan M. Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha 2 adrenoceptor properties. Eur J Clin Invest. 1985 Dec;15(6):341–348. doi: 10.1111/j.1365-2362.1985.tb00282.x. [DOI] [PubMed] [Google Scholar]
  6. Berlin I., Stalla-Bourdillon A., Thuillier Y., Turpin G., Puech A. J. Absence d'efficacité de la yohimbine dans le traitement de l'obésité. J Pharmacol. 1986 Jul-Sep;17(3):343–347. [PubMed] [Google Scholar]
  7. 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]
  8. Brodde O. E., Daul A., Wellstein A., Palm D., Michel M. C., Beckeringh J. J. Differentiation of beta 1- and beta 2-adrenoceptor-mediated effects in humans. Am J Physiol. 1988 Feb;254(2 Pt 2):H199–H206. doi: 10.1152/ajpheart.1988.254.2.H199. [DOI] [PubMed] [Google Scholar]
  9. Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. De Bruijne J. J. Biochemical observations during total starvation in dogs. Int J Obes. 1979;3(3):239–247. [PubMed] [Google Scholar]
  11. Fain J. N., Garcĩa-Sáinz J. A. Adrenergic regulation of adipocyte metabolism. J Lipid Res. 1983 Aug;24(8):945–966. [PubMed] [Google Scholar]
  12. Hedberg A., Minneman K. P., Molinoff P. B. Differential distribution of beta-1 and beta-2 adrenergic receptors in cat and guinea-pig heart. J Pharmacol Exp Ther. 1980 Mar;212(3):503–508. [PubMed] [Google Scholar]
  13. Hedler L., Stamm G., Weitzell R., Starke K. Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers. Eur J Pharmacol. 1981 Mar 5;70(1):43–52. doi: 10.1016/0014-2999(81)90430-1. [DOI] [PubMed] [Google Scholar]
  14. Henny C., Schutz Y., Buckert A., Meylan M., Jequier E., Felber J. P. Thermogenic effect of the new beta-adrenoreceptor agonist Ro 16-8714 in healthy male volunteers. Int J Obes. 1987;11(5):473–483. [PubMed] [Google Scholar]
  15. James W. P., Haraldsdottir J., Liddell F., Jung R. T., Shetty P. S. Autonomic responsiveness in obesity with and without hypertension. Int J Obes. 1981;5 Suppl 1:73–78. [PubMed] [Google Scholar]
  16. Jensen M. D., Haymond M. W., Gerich J. E., Cryer P. E., Miles J. M. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest. 1987 Jan;79(1):207–213. doi: 10.1172/JCI112785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johansson L. H., Persson H. Beta 2-adrenoceptors in guinea-pig atria. J Pharm Pharmacol. 1983 Dec;35(12):804–807. doi: 10.1111/j.2042-7158.1983.tb02900.x. [DOI] [PubMed] [Google Scholar]
  18. Kaumann A. J., Lemoine H. Direct labelling of myocardial beta 1-adrenoceptors. Comparison of binding affinity of 3H-(-)-bisoprolol with its blocking potency. Naunyn Schmiedebergs Arch Pharmacol. 1985 Oct;331(1):27–39. doi: 10.1007/BF00498849. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Lafontan M., Berlan M. Evidence for the alpha 2 nature of the alpha-adrenergic receptor inhibiting lipolysis in human fat cells. Eur J Pharmacol. 1980 Aug 22;66(1):87–93. doi: 10.1016/0014-2999(80)90298-8. [DOI] [PubMed] [Google Scholar]
  21. Lafontan M., Berlan M., Villeneuve A. Preponderance of alpha 2- over beta 1-adrenergic receptor sites in human fat cells is not predictive of the lipolytic effect of physiological catecholamines. J Lipid Res. 1983 Apr;24(4):429–440. [PubMed] [Google Scholar]
  22. Landsberg L., Young J. B. Fasting, feeding and regulation of the sympathetic nervous system. N Engl J Med. 1978 Jun 8;298(23):1295–1301. doi: 10.1056/NEJM197806082982306. [DOI] [PubMed] [Google Scholar]
  23. Langer S. Z. Presynaptic regulation of the release of catecholamines. Pharmacol Rev. 1980 Dec;32(4):337–362. [PubMed] [Google Scholar]
  24. Lilavivathana U., Campbell R. G., Brodows R. G. Control of insulin secretion during fasting in man. Metabolism. 1978 Jul;27(7):815–821. doi: 10.1016/0026-0495(78)90216-0. [DOI] [PubMed] [Google Scholar]
  25. Loubatières A., Mariani M. M., Sorel G., Savi L. The action of beta-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of beta receptor. Diabetologia. 1971 Jun;7(3):127–132. doi: 10.1007/BF01212541. [DOI] [PubMed] [Google Scholar]
  26. Mauriege P., Galitzky J., Berlan M., Lafontan M. Heterogeneous distribution of beta and alpha-2 adrenoceptor binding sites in human fat cells from various fat deposits: functional consequences. Eur J Clin Invest. 1987 Apr;17(2):156–165. doi: 10.1111/j.1365-2362.1987.tb02395.x. [DOI] [PubMed] [Google Scholar]
  27. Mauriège P., De Pergola G., Berlan M., Lafontan M. Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists. J Lipid Res. 1988 May;29(5):587–601. [PubMed] [Google Scholar]
  28. Milavec-Krizman M., Wagner H. Effects of the adrenergic agonists isoprenaline and noradrenaline and the alpha-blocking agents dihydroergotamine and phentolamine on the lipolysis in isolated fat cells of the rat, guinea pig, dog and man. Biochem Pharmacol. 1978;27(19):2305–2310. doi: 10.1016/0006-2952(78)90136-3. [DOI] [PubMed] [Google Scholar]
  29. O'Donnell S. R., Wanstall J. C. Evidence that ICI 118, 551 is a potent, highly Beta 2-selective adrenoceptor antagonist and can be used to characterize Beta-adrenoceptor populations in tissues. Life Sci. 1980 Aug 25;27(8):671–677. doi: 10.1016/0024-3205(80)90008-9. [DOI] [PubMed] [Google Scholar]
  30. O'Donnell S. R., Wanstall J. C. Responses to the beta 2-selective agonist procaterol of vascular and atrial preparations with different functional beta-adrenoceptor populations. Br J Pharmacol. 1985 Jan;84(1):227–235. [PMC free article] [PubMed] [Google Scholar]
  31. O'Donnell S. R., Wanstall J. C. pA2 values of selective beta-adrenoceptor antagonists on isolated atria demonstrate a species difference in the beta-adrenoceptor populations mediating chronotropic responses in cat and guinea-pig. J Pharm Pharmacol. 1979 Oct;31(10):686–690. doi: 10.1111/j.2042-7158.1979.tb13629.x. [DOI] [PubMed] [Google Scholar]
  32. Ostman J., Arner P., Kimura H., Wahrenberg H., Engfeldt P. Influence of fasting on lipolytic response to adrenergic agonists and on adrenergic receptors in subcutaneous adipocytes. Eur J Clin Invest. 1984 Oct;14(5):383–391. doi: 10.1111/j.1365-2362.1984.tb01199.x. [DOI] [PubMed] [Google Scholar]
  33. Papeschi R., Theiss P. The effect of yohimbine on the turnover of brain catecholamines and serotonin. Eur J Pharmacol. 1975 Aug;33(1):1–12. doi: 10.1016/0014-2999(75)90131-4. [DOI] [PubMed] [Google Scholar]
  34. Pfister S. L., Keeton T. K. The mechanism of yohimbine-induced renin release in the conscious rat. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):35–46. doi: 10.1007/BF00169474. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Rump L. C., Majewski H. Beta adrenoceptor facilitation of norepinephrine release is not dependent on local angiotensin II formation in the rat isolated kidney. J Pharmacol Exp Ther. 1987 Dec;243(3):1107–1112. [PubMed] [Google Scholar]
  37. Scheen A., Cession-Fossion A., Scheen-Lavigne M., Luyckx A. Diminution de la sécrétion d'adrénaline au cours de la diète hypocalorique protélique chez l'obèse. Ann Endocrinol (Paris) 1981 Dec;42(6):531–536. [PubMed] [Google Scholar]
  38. Stanton H. C., Brenner G., Mayfield E. D., Jr Studies on isoproterenol-induced cardiomegaly in rats. Am Heart J. 1969 Jan;77(1):72–80. doi: 10.1016/0002-8703(69)90131-8. [DOI] [PubMed] [Google Scholar]
  39. Starke K., Borowski E., Endo T. Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine. Eur J Pharmacol. 1975 Dec;34(2):385–388. doi: 10.1016/0014-2999(75)90268-x. [DOI] [PubMed] [Google Scholar]
  40. Stokholm K. H., Andersen T., Lindgreen P. Low serum free T3 concentrations in postobese patients previously treated with very-low-calorie diet. Int J Obes. 1987;11(1):85–92. [PubMed] [Google Scholar]
  41. Suda A. K., Pittman C. S., Shimizu T., Chambers J. B., Jr The production and metabolism of 3,5,3'-triiodothyronine and 3,3',5-triiodothyronine in normal and fasting subjects. J Clin Endocrinol Metab. 1978 Dec;47(6):1311–1319. doi: 10.1210/jcem-47-6-1311. [DOI] [PubMed] [Google Scholar]
  42. Taouis M., Berlan M., Montastruc P., Lafontan M. Characterization of dog fat cell adrenoceptors: variations in alpha-2 and beta adrenergic receptors distribution according to the extent of the fat deposits and the anatomical location. J Pharmacol Exp Ther. 1987 Sep;242(3):1041–1049. [PubMed] [Google Scholar]
  43. Valet P., Damase-Michel C., Chamontin B., Durand D., Chollet F., Montastruc J. L. Platelet alpha 2- and leucocyte beta 2-adrenoceptors in phaeochromocytoma: effect of tumour removal. Eur J Clin Invest. 1988 Oct;18(5):481–485. doi: 10.1111/j.1365-2362.1988.tb01043.x. [DOI] [PubMed] [Google Scholar]
  44. Wemer J., van der Lugt J. C., de Langen C. D., Mulder A. H. On the capacity of presynaptic alpha receptors to modulate norepinephrine release from slices of rat neocortex and the affinity of some agonists and antagonists for these receptors. J Pharmacol Exp Ther. 1979 Dec;211(3):445–451. [PubMed] [Google Scholar]
  45. Yabuuchi Y. The beta-adrenoceptor stimulant properties of OPC-2009 on guinea-pig isolated tracheal, right atrial and left atrial preparations. Br J Pharmacol. 1977 Dec;61(4):513–521. doi: 10.1111/j.1476-5381.1977.tb07543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Young J. B., Landsberg L. Suppression of sympathetic nervous system during fasting. Science. 1977 Jun 24;196(4297):1473–1475. doi: 10.1126/science.867049. [DOI] [PubMed] [Google Scholar]
  47. Zahorska-Markiewicz B., Kucio C., Piskorska D. Adrenergic control of lipolysis and metabolic responses in obesity. Horm Metab Res. 1986 Oct;18(10):693–697. doi: 10.1055/s-2007-1012409. [DOI] [PubMed] [Google Scholar]
  48. de Bruijne J. J., Altszuler N., Hampshire J., Visser T. J., Hackeng W. H. Fat mobilization and plasma hormone levels in fasted dogs. Metabolism. 1981 Feb;30(2):190–194. doi: 10.1016/0026-0495(81)90171-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES