Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1976 Jan 1;68(1):142–153. doi: 10.1083/jcb.68.1.142

Lanthanum: inhibition of ACTH-stimulated cyclic AMP and corticosterone synthesis in isolated rat adrenocortical cells

PMCID: PMC2109618  PMID: 173723

Abstract

Lanthanum (La+++) is a well-known Ca++ antagonist in a number of biological systems. It was used in the present study to examine the role of Ca++ in the regulation of adenyl cyclase of the adrenal cortex by ACTH. In micromolar concentrations, .La+++ inhibited both cyclic AMP and corticosterone response of isolated adrenal cortex cells to ACTH. However, a number of intracellular processes were not affected by La+++. These include the stimulation of steroidogenesis by dibutyryl cyclic AMP, conversion of several steroid precursors into corticosterone, and stimulation of the latter by glucose. Thus, inhibition of steroidogenesis by La+++ appears to be solely due to an inhibition of ACTH-stimulated cyclic AMP formation. Electron microscope examination showed that La+++ was localized on plasma membrane of the cells and did not appear to penetrate beyond this region. Since La+++ is believed to replace Ca++ at superficial binding sites on the cell membrane, it is proposed that Ca++ at these sites plays an important role in the regulation of adenyl cyclase by ACTH. Similarities in the role of Ca++ in "excitation-contraction" coupling and in the ACTH- adenyl cyclase system raise the possibility that a contractile protein may be involved in the regulation of adenyl cyclase by those hormones which are known to require Ca++ in the process.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Albano J. D., Barnes G. D., Maudsley D. V., Brown B. L., Etkins R. P. Factors affecting the saturation assay of cyclic AMP in biological systems. Anal Biochem. 1974 Jul;60(1):130–141. doi: 10.1016/0003-2697(74)90137-7. [DOI] [PubMed] [Google Scholar]
  2. BIRMINGHAM M. K., ELLIOTT F. H., VALERE P. H. The need for the presence of calcium for the stimulation in vitro of rat adrenal glands by adrenocorticotrophic hormone. Endocrinology. 1953 Dec;53(6):687–689. doi: 10.1210/endo-53-6-687. [DOI] [PubMed] [Google Scholar]
  3. Beall R. J., Sayers G. Isolated adrenal cells: steroidogenesis and cyclic AMP accumulation in response to ACTH. Arch Biochem Biophys. 1972 Jan;148(1):70–76. doi: 10.1016/0003-9861(72)90116-6. [DOI] [PubMed] [Google Scholar]
  4. Berl S., Puszkin S., Nicklas W. J. Actomyosin-like protein in brain. Science. 1973 Feb 2;179(4072):441–446. doi: 10.1126/science.179.4072.441. [DOI] [PubMed] [Google Scholar]
  5. Birnbaumer L., Pohl S. L., Michiel H., Krans M. J., Rodbell M. The actions of hormones on the adenyl cyclase system. Adv Biochem Psychopharmacol. 1970;3:185–208. [PubMed] [Google Scholar]
  6. Brightman M. W., Reese T. S. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol. 1969 Mar;40(3):648–677. doi: 10.1083/jcb.40.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown B. L., Ekins R. P., Albano J. D. Saturation assay for cyclic AMP using endogenous binding protein. Adv Cyclic Nucleotide Res. 1972;2:25–40. [PubMed] [Google Scholar]
  8. Bär H. P., Hechter O. Adenyl cyclase and hormone action. 3. Calcium requirement for ACTH stimulation of adenyl cyclase. Biochem Biophys Res Commun. 1969 Jun 6;35(5):681–686. doi: 10.1016/0006-291x(69)90459-8. [DOI] [PubMed] [Google Scholar]
  9. Cuatrecasas P. Membrane receptors. Annu Rev Biochem. 1974;43(0):169–214. doi: 10.1146/annurev.bi.43.070174.001125. [DOI] [PubMed] [Google Scholar]
  10. DOGGENWEILER C. F., FRENK S. STAINING PROPERTIES OF LANTHANUM ON CELL MEMBRANES. Proc Natl Acad Sci U S A. 1965 Feb;53:425–430. doi: 10.1073/pnas.53.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farese R. V. On the requirement for calcium during the steroidogenic effect of ACTH. Endocrinology. 1971 Oct;89(4):1057–1063. doi: 10.1210/endo-89-4-1057. [DOI] [PubMed] [Google Scholar]
  12. Foreman J. C., Mongar J. L. Dual effect of lanthanum on histamine release from mast cells. Nat New Biol. 1972 Dec 20;240(103):255–256. doi: 10.1038/newbio240255a0. [DOI] [PubMed] [Google Scholar]
  13. Garant P. R. The demonstration of complex gap junctions between the cells of the enamel organ with lanthanum nitrate. J Ultrastruct Res. 1972 Aug;40(3):333–348. doi: 10.1016/s0022-5320(72)90105-0. [DOI] [PubMed] [Google Scholar]
  14. Hagiwara S., Henkart M. P., Kidokoro Y. Excitation-contraction coupling in amphioxus muscle cells. J Physiol. 1971 Dec;219(1):233–251. doi: 10.1113/jphysiol.1971.sp009659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haksar A., Maudsley D. V., Kimmel G. L., Péron F. G., Robidoux W. F., Jr, Gagnon G. Adrenocorticotropin stimulation of cyclic adenosine 3', 5'-monophosphate formation in isolated rat adrenal cells. The role of membrane sialic acid. Biochim Biophys Acta. 1974 Sep 5;362(2):356–365. doi: 10.1016/0304-4165(74)90228-1. [DOI] [PubMed] [Google Scholar]
  16. Haksar A., Péron F. G. The role of calcium in the steroidogenic response of rat adrenal cells to adrenocorticotropic hormone. Biochim Biophys Acta. 1973 Jul 28;313(2):363–371. doi: 10.1016/0304-4165(73)90036-6. [DOI] [PubMed] [Google Scholar]
  17. Hurwitz L., Joiner P. D., Von Hagen S. Mechanical responses of intestinal smooth muscle in a calcium-free medium. Proc Soc Exp Biol Med. 1967 Jun;125(2):518–522. doi: 10.3181/00379727-125-32136. [DOI] [PubMed] [Google Scholar]
  18. Jaanus S. D., Carchman R. A., Rubin R. P. Further studies on the relationship between cycl AMP levels and adrenocortical activity. Endocrinology. 1972 Oct;91(4):887–895. doi: 10.1210/endo-91-4-887. [DOI] [PubMed] [Google Scholar]
  19. Kalix P. Uptake and release of calcium in rabbit vagus nerve. Pflugers Arch. 1971;326(1):1–14. doi: 10.1007/BF00586791. [DOI] [PubMed] [Google Scholar]
  20. Kelly L. A., Koritz S. B. Bovine adrenal cortical adenyl cyclase and its stimulation by adrenocorticotropic hormone and NaF. Biochim Biophys Acta. 1971 Apr 20;237(1):141–155. doi: 10.1016/0304-4165(71)90043-2. [DOI] [PubMed] [Google Scholar]
  21. Kimmel G. L., Péron F. G., Haksar A., Bedigian E., Robidoux W. F., Jr, Lin M. T. Ultrastructure, steroidogenic potential, and energy metabolism of the Snell adrenocortical carcinoma 494. A comparison with normal adrenocortical tissue. J Cell Biol. 1974 Jul;62(1):152–163. doi: 10.1083/jcb.62.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Langer G. A., Frank J. S. Lanthanum in heart cell culture. Effect on calcium exchange correlated with its localization. J Cell Biol. 1972 Sep;54(3):441–455. doi: 10.1083/jcb.54.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lawson D. M., Schmidt G. H. Effects of lanthanum on 45 Ca movements and oxytocin-induced milk ejection in mammary tissue. Proc Soc Exp Biol Med. 1972 Jun;140(2):481–484. doi: 10.3181/00379727-140-36485. [DOI] [PubMed] [Google Scholar]
  24. Lefkowitz R. J., Roth J., Pastan I. ACTH-receptor interaction in the adrenal: a model for the initial step in the action of hormones that stimulate adenyl cyclase. Ann N Y Acad Sci. 1971 Dec 30;185:195–209. doi: 10.1111/j.1749-6632.1971.tb45249.x. [DOI] [PubMed] [Google Scholar]
  25. Lefkowitz R. J., Roth J., Pastan I. Effects of calcium on ACTH stimulation of the adrenal: separation of hormone binding from adenyl cyclase activation. Nature. 1970 Nov 28;228(5274):864–866. doi: 10.1038/228864a0. [DOI] [PubMed] [Google Scholar]
  26. Lin M. T., Haksar A., Peron F. G. The role of the Krebs cycle in the generation of intramitochondrial reducing equivalents for the 11 beta-hydroxylation of deoxycorticosterone in isolated rat adrenal cells. Arch Biochem Biophys. 1974 Oct;164(2):429–439. doi: 10.1016/0003-9861(74)90052-6. [DOI] [PubMed] [Google Scholar]
  27. Mackie C., Richardson M. C., Schulster D. Kinetics and dose-response characteristics of adenosine 3',5'-monophosphate production by isolated rat adrenal cells stimulated with adrenocorticotrophic hormone. FEBS Lett. 1972 Jul 1;23(3):345–348. doi: 10.1016/0014-5793(72)80312-0. [DOI] [PubMed] [Google Scholar]
  28. Martinez-Palomo A., Benitez D., Alanis J. Selective deposition of lanthanum in mammalian cardiac cell membranes. Ultrastructural and electrophysiological evidence. J Cell Biol. 1973 Jul;58(1):1–10. doi: 10.1083/jcb.58.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Moyle W. R., Kong Y. C., Ramachandran J. Steroidogenesis and cyclic adenosine 3',5'-monophosphate accumulation in rat adrenal cells. Divergent effects of adrenocorticotropin and its o-nitrophenyl sulfenyl derivative. J Biol Chem. 1973 Apr 10;248(7):2409–2417. [PubMed] [Google Scholar]
  30. Olsen R. W. Filamentous protein model for cyclic AMP-mediated cell regulatory mechanisms. J Theor Biol. 1975 Feb;49(2):263–287. doi: 10.1016/0022-5193(75)90172-1. [DOI] [PubMed] [Google Scholar]
  31. PERON F. G., KORITZ S. B. On the exogenous requirements for the action of ACTH in vitro on rat adrenal glands. J Biol Chem. 1958 Jul;233(1):256–259. [PubMed] [Google Scholar]
  32. Painter R. G., Sheetz M., Singer S. J. Detection and ultrastructural localization of human smooth muscle myosin-like molecules in human non-muscle cells by specific antibodies. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1359–1363. doi: 10.1073/pnas.72.4.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Payton B. W., Bennett M. V., Pappas G. D. Permeability and structure of junctional membranes at an electrotonic synapse. Science. 1969 Dec 26;166(3913):1641–1643. doi: 10.1126/science.166.3913.1641. [DOI] [PubMed] [Google Scholar]
  34. Pollard T. D., Weihing R. R. Actin and myosin and cell movement. CRC Crit Rev Biochem. 1974 Jan;2(1):1–65. doi: 10.3109/10409237409105443. [DOI] [PubMed] [Google Scholar]
  35. Revel J. P., Karnovsky M. J. Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol. 1967 Jun;33(3):C7–C12. doi: 10.1083/jcb.33.3.c7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Rubin R. P., Carchman R. A., Jaanus S. D. Role of calcium and adenosine cyclic 3'-5' phosphate in action of adrenocorticotropin. Nat New Biol. 1972 Nov 29;240(100):150–152. doi: 10.1038/newbio240150a0. [DOI] [PubMed] [Google Scholar]
  38. SILBER R. H., BUSCH R. D., OSLAPAS R. Practical procedure for estimation of corticosterone or hydrocortisone. Clin Chem. 1958 Aug;4(4):278–285. [PubMed] [Google Scholar]
  39. Sanborn W. G., Langer G. A. Specific uncoupling of excitation and contraction in mammalian cardiac tissue by lanthanum. J Gen Physiol. 1970 Aug;56(2):191–217. doi: 10.1085/jgp.56.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sayers G., Beall R. J., Seelig S. Isolated adrenal cells: adrenocorticotropic hormone, calcium, steroidogenesis, and cyclic adenosine monophosphate. Science. 1972 Mar 10;175(4026):1131–1133. doi: 10.1126/science.175.4026.1131. [DOI] [PubMed] [Google Scholar]
  41. Seelig S., Sayers G. Isolated adrenal cortex cells: ACTH agonists, partial agonists, antagonists; cyclic AMP and corticosterone production. Arch Biochem Biophys. 1973 Jan;154(1):230–239. doi: 10.1016/0003-9861(73)90053-2. [DOI] [PubMed] [Google Scholar]
  42. Shea S. M. Lanthanum staining of the surface coat of cells. Its enhancement by the use of fixatives containing Alcian blue or cetylpyridinium chloride. J Cell Biol. 1971 Dec;51(3):611–620. doi: 10.1083/jcb.51.3.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  44. Singer S. J. The molecular organization of membranes. Annu Rev Biochem. 1974;43(0):805–833. doi: 10.1146/annurev.bi.43.070174.004105. [DOI] [PubMed] [Google Scholar]
  45. Weiss G. B., Goodman F. R. Effects of lanthanum on contraction, calcium distribution and Ca45 movements in intestinal smooth muscle. J Pharmacol Exp Ther. 1969 Sep;169(1):46–55. [PubMed] [Google Scholar]
  46. Weiss G. B. On the site of action of lanthanum in frog sartorius muscle. J Pharmacol Exp Ther. 1970 Sep;174(3):517–526. [PubMed] [Google Scholar]
  47. Zacks S. I., Saito A. Direct connections between the T system and the subneural apparatus in mouse neuromuscular junctions demonstrated by lanthanum. J Histochem Cytochem. 1970 Apr;18(4):302–304. doi: 10.1177/18.4.302. [DOI] [PubMed] [Google Scholar]
  48. van Breemen C., De Weer P. Lanthanum inhibition of 45Ca efflux from the squid giant axon. Nature. 1970 May 23;226(5247):760–761. doi: 10.1038/226760a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES