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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
. 1991 Dec 15;88(24):11124–11128. doi: 10.1073/pnas.88.24.11124

Receptors and neurosecretory actions of endothelin in hypothalamic neurons.

L Z Krsmanović 1, S S Stojilković 1, T Balla 1, S al-Damluji 1, R I Weiner 1, K J Catt 1
PMCID: PMC53086  PMID: 1662384

Abstract

Primary cultures of rat hypothalamic neurons were found to secrete the potent calcium-mobilizing and mitogenic peptide endothelin (ET) and to contain specific ET binding sites with higher affinity for ET-1 and ET-2 than ET-3. ET receptors of similar specificity were also identified in two gonadotropin-releasing hormone (GnRH) neuronal cell lines (GT1-1 and GT1-7). In both primary cultures and GnRH neurons, receptor binding of ETs led to marked and dose-dependent increases of inositol phosphates; inositol bis-, tris-, and tetrakisphosphates increased promptly, reached a peak within 2 min, and returned toward the steady-state levels during the next 10 min. ET-1 was more potent than ET-3 in mobilizing inositol phosphates, consistent with its greater affinity for the ET receptors in these cells. ET also stimulated GnRH secretion from perifused hypothalamic cultures and GnRH cell lines, with a sharp increase followed by a prompt decline to the basal level. These data show that ET is produced in the hypothalamus and acts through calcium-mobilizing ET receptors in normal and transformed secretory neurons to stimulate GnRH release. These actions of locally produced ETs upon GnRH-secreting neurons indicate that the vasoconstrictor peptides have the capacity to regulate neurosecretion and could participate in the hypothalamic control of anterior pituitary function and gonadotropin secretion.

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Selected References

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  1. Ambar I., Kloog Y., Kochva E., Wollberg Z., Bdolah A., Oron U., Sokolovsky M. Characterization and localization of a novel neuroreceptor for the peptide sarafotoxin. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1104–1110. doi: 10.1016/s0006-291x(88)80987-2. [DOI] [PubMed] [Google Scholar]
  2. Arai H., Hori S., Aramori I., Ohkubo H., Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990 Dec 20;348(6303):730–732. doi: 10.1038/348730a0. [DOI] [PubMed] [Google Scholar]
  3. Balla T., Guillemette G., Baukal A. J., Catt K. J. Metabolism of inositol 1,3,4-trisphosphate to a new tetrakisphosphate isomer in angiotensin-stimulated adrenal glomerulosa cells. J Biol Chem. 1987 Jul 25;262(21):9952–9955. [PubMed] [Google Scholar]
  4. Calvo J. J., Gonzalez R., De Carvalho L. F., Takahashi K., Kanse S. M., Hart G. R., Ghatei M. A., Bloom S. R. Release of substance P from rat hypothalamus and pituitary by endothelin. Endocrinology. 1990 May;126(5):2288–2295. doi: 10.1210/endo-126-5-2288. [DOI] [PubMed] [Google Scholar]
  5. Clarke M. J., Gillies G. E. Comparison of peptide release from fetal rat hypothalamic neurones cultured in defined media and serum-containing media. J Endocrinol. 1988 Mar;116(3):349–356. doi: 10.1677/joe.0.1160349. [DOI] [PubMed] [Google Scholar]
  6. Giaid A., Gibson S. J., Ibrahim B. N., Legon S., Bloom S. R., Yanagisawa M., Masaki T., Varndell I. M., Polak J. M. Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7634–7638. doi: 10.1073/pnas.86.19.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hartter D. E., Ramirez V. D. Responsiveness of immature versus adult male rat hypothalami to dibutyryl cyclic AMP- and forskolin-induced LHRH release in vitro. Neuroendocrinology. 1985 Jun;40(6):476–482. doi: 10.1159/000124118. [DOI] [PubMed] [Google Scholar]
  8. Hickey K. A., Rubanyi G., Paul R. J., Highsmith R. F. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol. 1985 May;248(5 Pt 1):C550–C556. doi: 10.1152/ajpcell.1985.248.5.C550. [DOI] [PubMed] [Google Scholar]
  9. Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K., Masaki T. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2863–2867. doi: 10.1073/pnas.86.8.2863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jones C. R., Hiley C. R., Pelton J. T., Mohr M. Autoradiographic visualization of the binding sites for [125I]endothelin in rat and human brain. Neurosci Lett. 1989 Feb 27;97(3):276–279. doi: 10.1016/0304-3940(89)90610-1. [DOI] [PubMed] [Google Scholar]
  11. Kloog Y., Bousso-Mittler D., Bdolah A., Sokolovsky M. Three apparent receptor subtypes for the endothelin/sarafotoxin family. FEBS Lett. 1989 Aug 14;253(1-2):199–202. doi: 10.1016/0014-5793(89)80958-5. [DOI] [PubMed] [Google Scholar]
  12. Koseki C., Imai M., Hirata Y., Yanagisawa M., Masaki T. Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide? Am J Physiol. 1989 Apr;256(4 Pt 2):R858–R866. doi: 10.1152/ajpregu.1989.256.4.R858. [DOI] [PubMed] [Google Scholar]
  13. Lee M. E., de la Monte S. M., Ng S. C., Bloch K. D., Quertermous T. Expression of the potent vasoconstrictor endothelin in the human central nervous system. J Clin Invest. 1990 Jul;86(1):141–147. doi: 10.1172/JCI114677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MacCumber M. W., Ross C. A., Glaser B. M., Snyder S. H. Endothelin: visualization of mRNAs by in situ hybridization provides evidence for local action. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7285–7289. doi: 10.1073/pnas.86.18.7285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MacCumber M. W., Ross C. A., Snyder S. H. Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2359–2363. doi: 10.1073/pnas.87.6.2359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marsault R., Vigne P., Breittmayer J. P., Frelin C. Astrocytes are target cells for endothelins and sarafotoxin. J Neurochem. 1990 Jun;54(6):2142–2144. doi: 10.1111/j.1471-4159.1990.tb04921.x. [DOI] [PubMed] [Google Scholar]
  17. Matsumoto H., Suzuki N., Onda H., Fujino M. Abundance of endothelin-3 in rat intestine, pituitary gland and brain. Biochem Biophys Res Commun. 1989 Oct 16;164(1):74–80. doi: 10.1016/0006-291x(89)91684-7. [DOI] [PubMed] [Google Scholar]
  18. Mellon P. L., Windle J. J., Goldsmith P. C., Padula C. A., Roberts J. L., Weiner R. I. Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron. 1990 Jul;5(1):1–10. doi: 10.1016/0896-6273(90)90028-e. [DOI] [PubMed] [Google Scholar]
  19. Peterfreund R. A., Vale W. High molecular weight somatostatin secretion by cultured rat brain cells. Brain Res. 1982 May 13;239(2):463–477. doi: 10.1016/0006-8993(82)90522-4. [DOI] [PubMed] [Google Scholar]
  20. Sakurai T., Yanagisawa M., Takuwa Y., Miyazaki H., Kimura S., Goto K., Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20;348(6303):732–735. doi: 10.1038/348732a0. [DOI] [PubMed] [Google Scholar]
  21. Shichiri M., Hirata Y., Kanno K., Ohta K., Emori T., Marumo F. Effect of endothelin-1 on release of arginine-vasopressin from perifused rat hypothalamus. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1332–1337. doi: 10.1016/0006-291x(89)91124-8. [DOI] [PubMed] [Google Scholar]
  22. Stojilković S. S., Dufau M. L., Catt K. J. Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. Endocrinology. 1987 Jul;121(1):384–394. doi: 10.1210/endo-121-1-384. [DOI] [PubMed] [Google Scholar]
  23. Stojilković S. S., Merelli F., Iida T., Krsmanović L. Z., Catt K. J. Endothelin stimulation of cytosolic calcium and gonadotropin secretion in anterior pituitary cells. Science. 1990 Jun 29;248(4963):1663–1666. doi: 10.1126/science.2163546. [DOI] [PubMed] [Google Scholar]
  24. Warner T. D., de Nucci G., Vane J. R. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol. 1989 Jan 17;159(3):325–326. doi: 10.1016/0014-2999(89)90167-2. [DOI] [PubMed] [Google Scholar]
  25. Yanagisawa M., Inoue A., Ishikawa T., Kasuya Y., Kimura S., Kumagaye S., Nakajima K., Watanabe T. X., Sakakibara S., Goto K. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6964–6967. doi: 10.1073/pnas.85.18.6964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]
  27. Yanagisawa M., Masaki T. Molecular biology and biochemistry of the endothelins. Trends Pharmacol Sci. 1989 Sep;10(9):374–378. doi: 10.1016/0165-6147(89)90011-4. [DOI] [PubMed] [Google Scholar]
  28. Yoshizawa T., Shinmi O., Giaid A., Yanagisawa M., Gibson S. J., Kimura S., Uchiyama Y., Polak J. M., Masaki T., Kanazawa I. Endothelin: a novel peptide in the posterior pituitary system. Science. 1990 Jan 26;247(4941):462–464. doi: 10.1126/science.2405487. [DOI] [PubMed] [Google Scholar]

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