Regulation of alpha-1 Adrenergic Receptors

  • Brian B. Hoffman
Part of the The Receptors book series (REC)


Catecholamines modulate a wide variety of important physiological processes, alpha-1 Adrenergic receptors play a major role in transducing many of the actions of catecholamines. A particularly prominent action of alpha-1 adrenergic receptors is the promotion of vasoconstriction in a range of vascular beds. Additionally these receptors are found in nonvascular smooth muscle such as vas deferens and uterus, as well as in other tissues such as the liver and heart. Although these receptors influence important cellular responses, it is clear that the physiological response to alpha-1 adrenergic receptor activation is not fixed, but may vary in a range of situations. For example, prolonged exposure to catecholamines may modify the effects of subsequent alpha-1 adrenergic receptor activation. Also, changes in hormonal state or disease processes such as hypertension may alter tissue responsiveness to alpha-1 adrenergic receptor-transduced events.


Vascular Smooth Muscle Adenylate Cyclase Adrenergic Receptor Smooth Muscle Contraction Glycogen Phosphorylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aggerbeck, M., Guellaen, G., and Hanoune, J. (1980) Adrenergic receptor of the alpha-1-subtype mediates the activation of the glycogen Phosphorylase in normal rat liver. Biochem. Pharmacol. 29, 1653–1662.PubMedCrossRefGoogle Scholar
  2. Aggerbeck, M., Ferry, N., Zafrani, E-S., Billon, M-C., Barouki, R., and Hanoune, J. (1983) Adrenergic regulation of glycogenosis in rat liver after cholestasis: Modulation of the balance between alpha-1 and beta-2 receptors. J. Clin. Invest. 71, 476–486.PubMedCrossRefGoogle Scholar
  3. Altura, B. M. (1972) Sex as a factor influencing the responsiveness of arterioles to catecholamines. Eur. J. Pharmacol. 20, 261–265.PubMedCrossRefGoogle Scholar
  4. Awad, R., Payne, R., and Deth, R. C. (1983) Alpha adrenergic receptor subtype associated with receptor binding, Ca++ influx, Ca++ release and contractile events in the rabbit aorta. J. Pharmacol Exp. Ther. 227, 60–67.PubMedGoogle Scholar
  5. Blair, J. B., James, M. E., and Foster, J. L. (1979a) Adrenergic control of glucose output and adenosine 3′:5′-monophosphate levels in hepatocytes from juvenile and adult rats. J. Biol. Chem. 254, 7579–7584.PubMedGoogle Scholar
  6. Blair, J. B., James, M. E., and Foster, J. L. (1979b) Adrenergic control of glycolysis and pyruvate kinase activity in hepatocytes from young and old rats. J. Biol. Chem. 254, 7585–7590.PubMedGoogle Scholar
  7. Bobik, A. (1982) Identification of alpha adrenoceptor subtypes in dog arteries by [3H]yohimbine and [3H]prazosin. Life Sci. 30, 219–228.PubMedCrossRefGoogle Scholar
  8. Bobik, A., Campbell, J. H., and Little, P. J. (1984) desensitization of the alpha-1 adrenoceptor system vascular smooth muscle. Biochem. Pharmacol. 33, 1143–1145.PubMedCrossRefGoogle Scholar
  9. Bohr, D. F. and Berecek, K. H. (1976) Relevance of vascular structural and smooth muscle sensitivity changes in hypertension. Aust. N.Z. of Med. (suppl. 2) 6, 26–34.CrossRefGoogle Scholar
  10. Boyd, H. and Martin, T. J. (1976) Changes in catecholamine- and glucagon-responsive adenylate cyclase activity in preneoplastic rat liver. Mol. Pharmacol. 12, 195–202.PubMedGoogle Scholar
  11. Carrier, O., Wedel, E. K., Barron, K. W. (1978) Specific alpha-adrenergic receptor desensitization in vascular smooth muscle. Blood Vess. 15, 247–258.Google Scholar
  12. Colucci, W. S. (1986) Adenosine 3′,5′-cyclic-monophosphate-dependent regulation of alpha-1 adrenergic receptor number in rabbit aortic smooth muscle cells. Circ. Res. 58, 292–297.PubMedGoogle Scholar
  13. Colucci, W. B., Gimbrone, M. A., Jr., Alexander, R. W. (1980) Characterization of post-synaptic alpha-adrenergic receptors by [3H]dihydro-ergocryptine binding in muscular arteries from the rat mesentery. Hypertension 2, 149–155.PubMedGoogle Scholar
  14. Colucci, W. B., Gimbrone, M. A., Jr., Alexander, R. W. (1981) Regulation of the post-synaptic alpha-adrenergic receptor in rat mesenteric artery: Effects of chemical sympathectomy and epinephrine treatment. Circ. Res. 48, 104–111.PubMedGoogle Scholar
  15. Colucci, W. S., Gimbrone, M. A., McLaughlin, M. K., Halpern, W., and Alexander, R. W. (1982) Increased vascular catecholamine sensitivity and alpha-adrenergic receptor affinity in female and estrogen-treated male rats. Circ. Res. 50, 805–811.PubMedGoogle Scholar
  16. Colucci, W. S., Brock, T. A., Gimbrone, M. A., Jr., and Alexander, R. W. (1984) Regulation of alpha-1 adrenergic receptor-coupled calcium flux in cultured vascular smooth muscle cells. Hypertension 6 (suppl. I), 119–124.Google Scholar
  17. Corvera, S. and Garcia-Sainz, J. A. (1983) Hypothyroidism abolishes the glycogenolytic effect of vasopressin, angiotensin II and A23187 but not that of alpha-1-adrenergic amines in rat hepatocytes. FEBS Lett. 153, 366–368.PubMedCrossRefGoogle Scholar
  18. Docherty, J. R., Constantine, J. W., and Starke, K. (1981) Smooth muscle of rabbit aorta contains alpha-1 but not alpha-2 adrenoceptors. Naunyn Schmiedebergs Arch. Pharmacol. 317, 5–7. PubMedCrossRefGoogle Scholar
  19. Exton, J. H. (1985) Role of calcium and phosphoinositides in the actions of certain hormones and neurotransmitters. J. Clin. Invest. 75, 1753–1757.PubMedCrossRefGoogle Scholar
  20. Folkow, B. (1971) The haemodynamic consequences of adaptive structural changes of the resistance vessels in hypertension. Clin. Sci. 41, 1–12.PubMedGoogle Scholar
  21. Furchgott, R. F. and Bhadrakom, S. (1953) Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrate and other drugs. J. Pharmacol. Exp. Ther. 108, 129–143.PubMedGoogle Scholar
  22. Guellaen, G., Yates-Aggerbeck, M., Vauquelin, G., Strosberg, D., and Ha-noune, J. (1978) Characterization with [3H]dihydroergocryptine of the alpha-adrenergic receptor of the hepatic plasma membrane. J. Bio. Chem. 253, 1114–1120.Google Scholar
  23. Harden, T. K. (1983) Agonist-induced desensitization of beta adrenergic receptor-linked adenylate cyclase. Pharmacol. Rev. 35, 5–32.PubMedGoogle Scholar
  24. Hoffman, B. B. and Lefkowitz, R. J. (1982) Adrenergic receptors in the heart. Ann. Rev. Physiol. 44, 475–484.CrossRefGoogle Scholar
  25. Hoffman, B. B., DeLean, A., Wood, C. L., Schocken, D. D., and Lefkowitz, R. J. (1979) Alpha adrenergic receptor subtypes: Quantitative assessment by ligand binding. Life Sci. 24, 1739–1746.PubMedCrossRefGoogle Scholar
  26. Hoffman, B. B., Michel, T., Kilpatrick, D. M., Lefkowitz, R. J., Tolbert, M. E. M., Gilman, H., and Fain, J. N. (1980) Agonist versus antagonist binding to alpha-adrenergic receptors. Proc. Natl. Acad. Sci. USA 77, 4569–4573.PubMedCrossRefGoogle Scholar
  27. Hoffman, B. B., Lavin, T. N., Lefkowitz, R. J., and Ruffolo, R. R., Jr. (1981) Alpha adrenergic receptor subtypes in rabbit uterus: Mediation of myometrial contraction and regulation by estrogens. J. Pharmacol. Exp. Ther. 219, 290–295.PubMedGoogle Scholar
  28. Itoh, H., Okajima, F., and Ui, M. (1984) Conversion of adrenergic mechaniam from an alpha- to a beta-type during primary culture of rat hepatocytes: Accompanying decreases in the function of the inhibitory nucleotide regulatory component of adenylate cyclase identified as the substate of islet-activating protein. J. Biol. Chem. 259, 15464–15473.PubMedGoogle Scholar
  29. Kunos, G., Vermes-Kunos, I., and Nickerson, M. (1974) Effects thyroid state on adrenoceptor properties. Nature 250, 779–781.PubMedCrossRefGoogle Scholar
  30. Kunos, G., Hirata, F., Ishac, E. J. N., and Tchakarov, L. (1984) Time-dependent conversion of alphax to beta-adrenoceptor-mediated glycogenolysis in isolated rat liver cells: Role of membrane phospholipase A2. Proc. Natl. Acad. Sci. USA 81, 6178–6182.PubMedCrossRefGoogle Scholar
  31. Kwan, C. Y., Garfield, R., and Daniel, E. E. (1979) An improved procedure for the isolation of plasma membranes from rat mesenteric arteries. J. Mol. Cell. Cardiol. 11, 639–659.PubMedCrossRefGoogle Scholar
  32. Latifpour, J. and Bylund, D. B. (1983) Characterization of adrenergic receptor binding in rat lung: Physiological regulation. J. Pharmacol. Exp. Ther. 224, 186–192.PubMedGoogle Scholar
  33. Lautt, W. W. (1980) Hepatic nerves: A review of their functions and effects. Can. J. Physiol. Pharmacol. 58, 105–123.PubMedCrossRefGoogle Scholar
  34. Lavin, T. N., Hoffman, B. B., and Lefkowitz, R. J. (1981) Determination of subtype selectivity of alpha-adrenergic antagonists: Comparison of selective and nonselective radioligands. Mol. Pharmacol. 20, 28–34.PubMedGoogle Scholar
  35. Leeb-Lundberg, L. M. F., Cotecchia, S., Lomasney, J. N., DeBernardis, J. F., Lefkowitz, R. J., and Caron, M. G. (1985) Phorbol esters promote alpha-1-adrenergic receptor-phosphorylation and receptor uncoupling from inositol phospholipid metabolism. Proc. Natl. Acad. Sci. USA 82, 5651–5655.PubMedCrossRefGoogle Scholar
  36. Lefkowitz, R. J., Stadel, J. M., and Caron, M. G. (1983) Adenylate cyclase coupled beta-adrenergic receptors: Structure and mechanisms of activation and desensitization. Ann. Rev. Biochem. 52, 159–186.PubMedCrossRefGoogle Scholar
  37. Levin, R. M., Shofer, F. S., and Wein, A. J. (1980) Estrogen-induced alterations in the autonomic responses of the rabbit urinary bladder. J. Pharmacol. Exp. Ther. 215, 614–618.PubMedGoogle Scholar
  38. Lurie, K., Tsujimoto, G., and Hoffman, B. (1985) Desensitization of alpha1 adrenergic receptor-mediated vascular smooth muscle contraction. J. Pharmacol. Exp. Ther. 234, 147–152.PubMedGoogle Scholar
  39. Malbon, C. C. (1980) Liver cell adenylate cyclase and beta-adrenergic receptors: Increased beta-adrenergic receptor number and responsiveness in the hypothyroid rat. J. Biol. Chem. 255, 8692–8699.PubMedGoogle Scholar
  40. Marshall, J. M. (1973) Effects of catecholamines on the smooth muscle of the female reproductive tract. Ann. Rev. Pharmacol. 13, 19–32.PubMedCrossRefGoogle Scholar
  41. Maze, M., Spiss, C. K., Tsujimoto, G., and Hoffman, B. B. (1985) Epinephrine infusion induces hyporesponsiveness of vascular smooth muscle. Life Sci. 37, 1571–1578.PubMedCrossRefGoogle Scholar
  42. McMillian, M. K., Schanberg, S. M., and Kuhn, C. M. (1983) Ontogeny of rat hepatic adrenoceptors. J. Pharmacol. Exp. Ther. 227, 181–186.PubMedGoogle Scholar
  43. Morgan, N. G., Blackmore, P. F., and Exton, J. H. (1983) Age-related changes in the control of hepatic cyclic AMP levels by alpha-1- and beta-2-adrenergic receptors in male rats. J. Biol. Chem. 258, 5103–5109.PubMedGoogle Scholar
  44. Nakamura, T., Tomomura, A., Noda, C., Shimoji, M., and Ichihara, A. (1983) Acquisition of beta-adrenergic response by adult hepatocytes during primary culture. J. Biol. Chem. 258, 9283–9289.PubMedGoogle Scholar
  45. Nakamura, T., Tomomura, A., Kato, S., Noda, C., and Ichihara, A. (1984) Reciprocal expressions of alpha1 and beta-adrenergic receptors, but constant expression of glucagon receptor by rat hepatocytes during development and primary culture. J. Biochem. 96, 127–136.PubMedGoogle Scholar
  46. Okajima, F. and Ui, M. (1982) Conversion of adrenergic regulation of glycogen Phosphorylase and synthase from an alpha to a beta type during primary culture of rat hepatocytes. Arch. Biochem. Biophys. 213, 658–668.PubMedCrossRefGoogle Scholar
  47. Preiksaitis, H. G. and Kunos, G. (1979) Adrenoceptor-mediated activation of liver glycogen Phosphorylase: Effects of thyroid state. Life Sci. 24, 35–42.PubMedCrossRefGoogle Scholar
  48. Preiksaitis, H. G., Kan, W. H., and Kunos, G. (1982) Decreased alpha-1-adrenoceptor responsiveness and density in liver cells of thyroidectomized rats. J. Biol. Chem. 257, 4321–4327.PubMedGoogle Scholar
  49. Refsnes, M., Sandnes, D., Melien, O., Sand, T. E., Jacobsen, S., and Christoffersen, T. (1983) Mechanisms for the emergence of catecholamine-sensitive adenyl ate cyclase and beta-adrenergic receptors in cultured hepatocytes. FEBS Lett. 164, 291–297.PubMedCrossRefGoogle Scholar
  50. Roberts, J. M., Insel, P. A., Goldfein, R. D., and Goldfein, A. (1977) Alpha adrenoceptors but not beta adrenoceptors increase in rabbit uterus with estrogen. Nature 270, 624–625.PubMedCrossRefGoogle Scholar
  51. Roberts, J. M., Insel, P. A., and Goldfein, A. (1981) Regulation of myometrial adrenoceptors and adrenergic response by sex steroids. Mol. Pharmacol. 20, 52–58.PubMedGoogle Scholar
  52. Rosenbaum,, J. S., Zera, P., Umans, V. A., Ginsburg, R., and Hoffman, B. B. (1986) Desensitization of aortic smooth muscle contraction in rats harboring pheochromocytoma. J. Pharm. Exp. Ther. 238, 396–400.Google Scholar
  53. Ruffolo, R. R., Jr., and Kopia, G. A. (1986) Importance of receptor regulation in the pathophysiology and therapy of congestive heart failure. Am. J. Med., in press.Google Scholar
  54. Schmelck, P-H. and Hanoune, J. (1980) The hepatic adrenergic receptors. Mol. Cell. Biochem. 33, 35–48.PubMedCrossRefGoogle Scholar
  55. Schmelck, P., Billon, M. C., Munnich, A., Geynet, P., Houssin, D., and Hanoune, J. (1979) The effects of common bile duct ligation upon the rat liver beta-adrenergic receptor adenylate cyclase system. FEBS Lett. 107, 259–263.PubMedCrossRefGoogle Scholar
  56. Schwarz, K. R., Lanier, S. M., Carter, E. A., Homey, C. J., and Graham, R. M. (1985) Rapid reciprocal changes in adrenergic receptors in intact isolated hepatocytes during primary cell culture. Mol. Pharmacol. 27, 200–209.PubMedGoogle Scholar
  57. Sherline, P., Eisen, H., and Glinsmann, W. (1974) Acute hormonal regulation of cyclic AMP content and glycogen Phosphorylase activity in fetal liver in organ culture. Endocrinology 94, 935–939.PubMedCrossRefGoogle Scholar
  58. Smith, J. M., Jones, S. B., Bylund, D. B., and Jones, A. W. (1986) Characterization of alpha-1 adrenergic receptors in the thoracic aorta of control and aldosterone hypertensive rats: Correlation of radioligand binding with potassium efflux and contraction. J. Pharmacol. Exp. Ther., in press.Google Scholar
  59. Snavely, M. D., Mahan, L. C., O’Connor, D. T., and Insel, P. A. (1983) Selective down-regulation of adrenergic receptor subtypes in tissues from rats with pheochromocytoma, Endocrinology 113, 354–361.PubMedCrossRefGoogle Scholar
  60. Studer, R. K., and Borle, A. B. (1982) Differences between male and female rats in the regulation of hepatic glycogenolysis. J. Physiol. Chem. 257, 7987–7993.Google Scholar
  61. Su, Y. F., Cubeddu, L., and Perkins, J. P. (1976) Regulation of adenosine 3’:5’-monophosphate content of human astrocytoma cells: Desensitization to catecholamines and prostaglandins. J. Cycl. Nucleotide Res. 2, 257–270.Google Scholar
  62. Sugden, D. and Klein, D. C. (1985) Regulation of rat pineal alpha-1 adrenoceptors. J. Neurochem. 44, 63–67.CrossRefGoogle Scholar
  63. Tsai, B. S. and Lefkowitz, R. J. (1978) [3H]Dihydroergocryptine binding to alpha adrenergic receptors in canine aortic membranes. J. Pharmacol. Exp. Ther. 204, 606–614.PubMedGoogle Scholar
  64. Tsujimoto, G., Bristow, M. R., and Hoffman, B. B. (1984) Identification of alpha1 adrenergic receptors in rabbit aorta with [125I]BE-2254. Life Sci. 34, 639–646.PubMedCrossRefGoogle Scholar
  65. Tsujimoto, A., Tsujimoto, G., and Hoffman, B. B. (1986a) Age-related change in adrenergic regulation of glycogen Phosphorylase in rat hepatocytes. Mechan. Aging Devel. 33, 167–175.CrossRefGoogle Scholar
  66. Tsujimoto, A., Tsujimoto, G., Azhar, S., and Hoffman, B. B. (1986b) Altered responsiveness to alpha and beta adrenoceptor stimulation in hepatocytes cultured in defined media. Biochem. Pharmacol. 35, 1400–1404.PubMedCrossRefGoogle Scholar
  67. Villalobos-Molina, R., Mirna, U. C., Hong, E., and Garcia-Sainz, J. A. (1982) Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: Effect of alpha1 adrenergic activation. J. Pharmacol. Exp. Ther. 222, 258–261.PubMedGoogle Scholar
  68. Wei, J. W., Ganis, R. A., Daniel, E. E. (1976) Isolation and characterization of plasma membrane from rat mesenteric arteries. Blood Vess. 13, 279–292.Google Scholar
  69. Weiss, R. J., Webb, R. C., and Smith, C. B. (1983) Alpha2 adrenoceptors on arterial smooth muscle: Selective labeling by [3H]Clonidine. J. Pharmacol. Exp. Ther. 225, 599–605.PubMedGoogle Scholar
  70. Wikberg, J. E. S., Akers, M., Caron, M. G., and Hagen, P.-O. (1983) Nor-epinephrine-induced down regulation of alpha1 adrenergic receptors in cultured rabbit aorta smooth muscle cells. Life Sci. 33, 1409–1417.PubMedCrossRefGoogle Scholar
  71. Williams, L. T. and Lefkowitz, R. J. (1977) Regulation of rabbit myometial alpha adrenergic receptors by estrogen and progesterone. J. Clin. Invest. 60, 815–818.PubMedCrossRefGoogle Scholar
  72. Wolfe, B. B., Harden, T. K., and Molinoff, P. B. (1976) Beta-adrenergic receptors in rat liver: Effects of adrenalectomy. Proc. Natl. Acad. Sci. USA 73, 1343–1347.PubMedCrossRefGoogle Scholar
  73. Wright, G. H. (1977) Changes in plasma membrane enzyme activities during regeneration in the rat. Biochim. Biophys. Acta 470, 368–381.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1987

Authors and Affiliations

  • Brian B. Hoffman

There are no affiliations available

Personalised recommendations