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




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]