Abstract
The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy.
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Selected References
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- Aurbach G. D., Fedak S. A., Woodard C. J., Palmer J. S., Hauser D., Troxler F. Beta-adrenergic receptor: stereospecific interaction of iodinated beta-blocking agent with high affinity site. Science. 1974 Dec 27;186(4170):1223–1224. doi: 10.1126/science.186.4170.1223. [DOI] [PubMed] [Google Scholar]
- Berg D. K., Kelly R. B., Sargent P. B., Williamson P., Hall Z. W. Binding of -bungarotoxin to acetylcholine receptors in mammalian muscle (snake venom-denervated muscle-neonatal muscle-rat diaphragm-SDS-polyacrylamide gel electrophoresis). Proc Natl Acad Sci U S A. 1972 Jan;69(1):147–151. doi: 10.1073/pnas.69.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bitensky M. W., Russell V., Blanco M. Independent variation of glucagon and epinephrine responsive components of hepatic adenyl cyclase as a function of age, sex and steroid hormones. Endocrinology. 1970 Jan;86(1):154–159. doi: 10.1210/endo-86-1-154. [DOI] [PubMed] [Google Scholar]
- Brimijoin S., Pluchino S., Trendelenburg U. On the mechanism of supersensitivity to norepinephrine in the denervated cat spleen. J Pharmacol Exp Ther. 1970 Nov;175(2):503–513. [PubMed] [Google Scholar]
- Brown E. M., Aurbach G. D. Beta-Adrenergic receptor interactions. Characterization of iodohydroxybenzylpindolol as a specific ligand. J Biol Chem. 1976 Mar 10;251(5):1232–1238. [PubMed] [Google Scholar]
- Cuatrecasas P., Tell G. P., Sica V., Parikh I., Chang K. J. Noradrenaline binding and the search for catecholamine receptors. Nature. 1974 Jan 11;247(5436):92–97. doi: 10.1038/247092a0. [DOI] [PubMed] [Google Scholar]
- Deguchi T., Axelrod J. Superinduction of serotonin N-acetyltransferase and supersensitivity of adenyl cyclase to catecholamines in denervated pineal gland. Mol Pharmacol. 1973 Sep;9(5):612–618. [PubMed] [Google Scholar]
- Dunnick J. K., Marinetti G. V. Hormone action at the membrane level. 3. Epinephrine interaction with the rat liver plasma membrane. Biochim Biophys Acta. 1971 Oct 12;249(1):122–134. doi: 10.1016/0005-2736(71)90089-7. [DOI] [PubMed] [Google Scholar]
- Exton J. H., Friedmann N., Wong E. H., Brineaux J. P., Corbin J. D., Park C. R. Interaction of glucocorticoids with glucagon and epinephrine in the control of gluconeogenesis and glycogenolysis in liver and of lipolysis in adipose tissue. J Biol Chem. 1972 Jun 10;247(11):3579–3588. [PubMed] [Google Scholar]
- Harden T. K., Wolfe B. B., Molinoff P. B. Binding of iodinated beta adrenergic antagonists to proteins derived from rat heart. Mol Pharmacol. 1976 Jan;12(1):1–15. [PubMed] [Google Scholar]
- KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kalisker A., Rutledge C. O., Perkins J. P. Effect of nerve degeneration by 6-hydroxydopamine on catecholamine-stimulated adenosine 3',5'-monophosphate formation in rat cerebral cortex. Mol Pharmacol. 1973 Sep;9(5):619–629. [PubMed] [Google Scholar]
- Kebabian J. W., Zatz M., Romero J. A., Axelrod J. Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3735–3739. doi: 10.1073/pnas.72.9.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
- 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]
- Lacombe M. L., Hanoune J. Enhanced specificity of epinephrine binding by rat liver plasma membranes in the presence of EDTA. Biochem Biophys Res Commun. 1974 Jun 4;58(3):667–673. doi: 10.1016/s0006-291x(74)80470-5. [DOI] [PubMed] [Google Scholar]
- Lefkowitz R. J., Mukherjee C., Coverstone M., Caron M. G. Stereospecific (3H)(minus)-alprenolol binding sites, beta-adrenergic receptors and adenylate cyclase. Biochem Biophys Res Commun. 1974 Sep 23;60(2):703–709. doi: 10.1016/0006-291x(74)90297-6. [DOI] [PubMed] [Google Scholar]
- Leray F., Chambaut A. M., Perrenoud M. L., Hanoune J. Adenylate-cyclase activity of rat-liver plasma membranes. Hormonal stimulation and effect of adrenalectomy. Eur J Biochem. 1973 Sep 21;38(1):185–192. doi: 10.1111/j.1432-1033.1973.tb03049.x. [DOI] [PubMed] [Google Scholar]
- Levitzki A., Atlas D., Steer M. L. The binding characteristics and number of beta-adrenergic receptors on the turkey erythrocyte. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2773–2776. doi: 10.1073/pnas.71.7.2773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maguire M. E., Wiklund R. A., Anderson H. J., Gilman A. G. Binding of (125I)iodohydroxybenzylpindolol to putative beta-adrenergic receptors of rat glioma cells and other cell clones. J Biol Chem. 1976 Mar 10;251(5):1221–1231. [PubMed] [Google Scholar]
- Mickey J., Tate R., Lefkowitz R. J. Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. J Biol Chem. 1975 Jul 25;250(14):5727–5729. [PubMed] [Google Scholar]
- Miledi R., Potter L. T. Acetylcholine receptors in muscle fibres. Nature. 1971 Oct 29;233(5322):599–603. doi: 10.1038/233599a0. [DOI] [PubMed] [Google Scholar]
- Mukherjee C., Caron M. G., Lefkowitz R. J. Catecholamine-induced subsensitivity of adenylate cyclase associated with loss of beta-adrenergic receptor binding sites. Proc Natl Acad Sci U S A. 1975 May;72(5):1945–1949. doi: 10.1073/pnas.72.5.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neville D. M., Jr Isolation of an organ specific protein antigen from cell-surface membrane of rat liver. Biochim Biophys Acta. 1968 Apr 9;154(3):540–552. doi: 10.1016/0005-2795(68)90014-7. [DOI] [PubMed] [Google Scholar]
- Palmer G. C., Spurgeon H. A., Priola D. V. Involvement of adenylate cyclase in mechanisms of denervation supersensitivity following surgical denervation of the dog heart. J Cyclic Nucleotide Res. 1975;1(2):89–95. [PubMed] [Google Scholar]
- Pilkis S. J., Claus T. H., Johnson R. A., Park C. R. Hormonal control of cyclic 3':5'-AMP levels and gluconeogenesis in isolated hepatocytes from fed rats. J Biol Chem. 1975 Aug 25;250(16):6328–6336. [PubMed] [Google Scholar]
- Rajerison R., Marchetti J., Roy C., Bockaert J., Jard S. The vasopressin-sensitive adenylate cyclase of the rat kidney. Effect of adrenalectomy and corticosteroids on hormonal receptor-enzyme coupling. J Biol Chem. 1974 Oct 25;249(20):6390–6400. [PubMed] [Google Scholar]
- Robison G. A., Butcher R. W., Sutherland E. W. Adenyl cyclase as an adrenergic receptor. Ann N Y Acad Sci. 1967 Feb 10;139(3):703–723. doi: 10.1111/j.1749-6632.1967.tb41239.x. [DOI] [PubMed] [Google Scholar]
