Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jan;87(2):623–627. doi: 10.1073/pnas.87.2.623

Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone.

P K Pang 1, R Wang 1, J Shan 1, E Karpinski 1, C G Benishin 1
PMCID: PMC53317  PMID: 1689047

Abstract

The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca2+ channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca2+ currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca2+ channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca2+ in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues, PTH can act as an endogenous blocker of Ca2+ entry.

Full text

PDF
623

Images in this article

Selected References

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

  1. Bean B. P., Sturek M., Puga A., Hermsmeyer K. Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs. Circ Res. 1986 Aug;59(2):229–235. doi: 10.1161/01.res.59.2.229. [DOI] [PubMed] [Google Scholar]
  2. Berthelot A., Gairard A. Effet de la parathormone sur la pression artérielle et la contraction de l'aorte isolée de rat. Experientia. 1975 Apr 15;31(4):457–458. doi: 10.1007/BF02026377. [DOI] [PubMed] [Google Scholar]
  3. Caffrey J. M., Josephson I. R., Brown A. M. Calcium channels of amphibian stomach and mammalian aorta smooth muscle cells. Biophys J. 1986 Jun;49(6):1237–1242. doi: 10.1016/S0006-3495(86)83753-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Godfraind T. Calcium exchange in vascular smooth muscle, action of noradrenaline and lanthanum. J Physiol. 1976 Aug;260(1):21–35. doi: 10.1113/jphysiol.1976.sp011501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  6. HANDLER P., COHN D. V. Effect of parathyroid extract on renal function. Am J Physiol. 1952 Apr;169(1):188–193. doi: 10.1152/ajplegacy.1952.169.1.188. [DOI] [PubMed] [Google Scholar]
  7. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  8. Helwig J. J., Schleiffer R., Judes C., Gairard A. Distribution of parathyroid hormone-sensitive adenylate cyclase in isolated rabbit renal cortex microvessels and glomeruli. Life Sci. 1984 Dec 24;35(26):2649–2657. doi: 10.1016/0024-3205(84)90034-1. [DOI] [PubMed] [Google Scholar]
  9. Hester R. K., Weiss G. B., Fry W. J. Differing actions of nitroprusside and D-600 on tension and 45Ca fluxes in canine renal arteries. J Pharmacol Exp Ther. 1979 Jan;208(1):155–160. [PubMed] [Google Scholar]
  10. Ives H. E., Schultz G. S., Galardy R. E., Jamieson J. D. Preparation of functional smooth muscle cells from the rabbit aorta. J Exp Med. 1978 Nov 1;148(5):1400–1413. doi: 10.1084/jem.148.5.1400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimhi Y., Palfrey C., Spector I., Barak Y., Littauer U. Z. Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. Proc Natl Acad Sci U S A. 1976 Feb;73(2):462–466. doi: 10.1073/pnas.73.2.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kondo N., Shibata S., Tenner T. E., Jr, Pang P. K. Electromechanical effects of bPTH-(1-34) on rabbit sinus node cells and guinea pig papillary muscles. J Cardiovasc Pharmacol. 1988 May;11(5):619–625. doi: 10.1097/00005344-198805000-00016. [DOI] [PubMed] [Google Scholar]
  13. Lack E. E., Delay S., Linnoila R. I. Ectopic parathyroid tissue within the vagus nerve. Incidence and possible clinical significance. Arch Pathol Lab Med. 1988 Mar;112(3):304–306. [PubMed] [Google Scholar]
  14. Moolenaar W. H., Spector I. Ionic currents in cultured mouse neuroblastoma cells under voltage-clamp conditions. J Physiol. 1978 May;278:265–286. doi: 10.1113/jphysiol.1978.sp012303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Narahashi T., Tsunoo A., Yoshii M. Characterization of two types of calcium channels in mouse neuroblastoma cells. J Physiol. 1987 Feb;383:231–249. doi: 10.1113/jphysiol.1987.sp016406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nickols G. A. Increased cyclic AMP in cultured vascular smooth muscle cells and relaxation of aortic strips by parathyroid hormone. Eur J Pharmacol. 1985 Oct 8;116(1-2):137–144. doi: 10.1016/0014-2999(85)90194-3. [DOI] [PubMed] [Google Scholar]
  17. Nissenson R. A., Teitelbaum A. P., Arnaud C. D. Assay for parathyroid hormone receptors. Methods Enzymol. 1985;109:48–56. doi: 10.1016/0076-6879(85)09075-9. [DOI] [PubMed] [Google Scholar]
  18. Pang P. K., Tenner T. E., Jr, Yee J. A., Yang M., Janssen H. F. Hypotensive action of parathyroid hormone preparations on rats and dogs. Proc Natl Acad Sci U S A. 1980 Jan;77(1):675–678. doi: 10.1073/pnas.77.1.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pang P. K., Yang M. C., Keutmann H. T., Kenny A. D. Structure activity relationship of parathyroid hormone: separation of the hypotensive and the hypercalcemic properties. Endocrinology. 1983 Jan;112(1):284–289. doi: 10.1210/endo-112-1-284. [DOI] [PubMed] [Google Scholar]
  20. Pang P. K., Yang M. C., Sham J. S. Parathyroid hormone and calcium entry blockade in a vascular tissue. Life Sci. 1988;42(14):1395–1400. doi: 10.1016/0024-3205(88)90169-5. [DOI] [PubMed] [Google Scholar]
  21. Pang P. K., Yang M. C., Tenner T. E., Jr, Chang J. K., Shimizu M. Hypotensive action of synthetic fragments of parathyroid hormone. J Pharmacol Exp Ther. 1981 Mar;216(3):567–571. [PubMed] [Google Scholar]
  22. Tenner T. E., Jr, Ramanadham S., Yang M. C., Pang P. K. Chronotropic actions of bPTH-(1-34) in the right atrium of the rat. Can J Physiol Pharmacol. 1983 Oct;61(10):1162–1167. doi: 10.1139/y83-173. [DOI] [PubMed] [Google Scholar]
  23. Wang R., Karpinski E., Pang P. K. Two types of calcium channels in isolated smooth muscle cells from rat tail artery. Am J Physiol. 1989 May;256(5 Pt 2):H1361–H1368. doi: 10.1152/ajpheart.1989.256.5.H1361. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES