Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):141–147. doi: 10.1172/JCI114677

Expression of the potent vasoconstrictor endothelin in the human central nervous system.

M E Lee 1, S M de la Monte 1, S C Ng 1, K D Bloch 1, T Quertermous 1
PMCID: PMC296701  PMID: 2195059

Abstract

Endothelin is a potent vasoconstrictive peptide initially characterized as a product of endothelial cells. To examine the potential role of endothelin as a neuropeptide, we studied its distribution in the human central nervous system. RNA blot hybridization provided evidence of endothelin gene transcription in a variety of functional regions of the brain. In situ hybridization confirmed the widespread pattern of endothelin transcription and indicated that the highest density of cells containing endothelin mRNA is in the hypothalamus. This technique localized endothelin transcription to cells of the nervous system as well as the vascular endothelium. Immunocytochemical studies detected endothelin immunoreactivity in neurons, providing evidence of the synthesis of the peptide in this cell type and confirming that endothelin is a neuropeptide. Although the prominent expression of endothelin in the hypothalamus may indicate a central vasoregulatory role for the peptide, the widespread distribution of endothelin in neurons in other areas of the brain implies a more fundamental role in the regulation of nervous system function.

Full text

PDF
141

Images in this article

142Image
on p.142
142Image
on p.142
143Image
on p.143
143Image
on p.143
143Image
on p.143
144Image
on p.144
144Image
on p.144
144Image
on p.144
144Image
on p.144
144Image
on p.144
145Image
on p.145
145Image
on p.145
145Image
on p.145
145Image
on p.145
145Image
on p.145

Selected References

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

  1. Badr K. F., Murray J. J., Breyer M. D., Takahashi K., Inagami T., Harris R. C. Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Elucidation of signal transduction pathways. J Clin Invest. 1989 Jan;83(1):336–342. doi: 10.1172/JCI113880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bloch K. D., Eddy R. L., Shows T. B., Quertermous T. cDNA cloning and chromosomal assignment of the gene encoding endothelin 3. J Biol Chem. 1989 Oct 25;264(30):18156–18161. [PubMed] [Google Scholar]
  3. Bloch K. D., Friedrich S. P., Lee M. E., Eddy R. L., Shows T. B., Quertermous T. Structural organization and chromosomal assignment of the gene encoding endothelin. J Biol Chem. 1989 Jun 25;264(18):10851–10857. [PubMed] [Google Scholar]
  4. De la Monte S. M., Federoff H. J., Ng S. C., Grabczyk E., Fishman M. C. GAP-43 gene expression during development: persistence in a distinctive set of neurons in the mature central nervous system. Brain Res Dev Brain Res. 1989 Apr 1;46(2):161–168. doi: 10.1016/0165-3806(89)90279-4. [DOI] [PubMed] [Google Scholar]
  5. Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [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. Goto K., Kasuya Y., Matsuki N., Takuwa Y., Kurihara H., Ishikawa T., Kimura S., Yanagisawa M., Masaki T. Endothelin activates the dihydropyridine-sensitive, voltage-dependent Ca2+ channel in vascular smooth muscle. Proc Natl Acad Sci U S A. 1989 May;86(10):3915–3918. doi: 10.1073/pnas.86.10.3915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Komuro I., Kurihara H., Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett. 1988 Oct 10;238(2):249–252. doi: 10.1016/0014-5793(88)80489-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Krieger D. T. Brain peptides: what, where, and why? Science. 1983 Dec 2;222(4627):975–985. doi: 10.1126/science.6139875. [DOI] [PubMed] [Google Scholar]
  12. Lind R. W., Swanson L. W., Ganten D. Angiotensin II immunoreactivity in the neural afferents and efferents of the subfornical organ of the rat. Brain Res. 1984 Nov 12;321(2):209–215. doi: 10.1016/0006-8993(84)90174-4. [DOI] [PubMed] [Google Scholar]
  13. Lynch D. C., Zimmerman T. S., Collins C. J., Brown M., Morin M. J., Ling E. H., Livingston D. M. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell. 1985 May;41(1):49–56. doi: 10.1016/0092-8674(85)90060-1. [DOI] [PubMed] [Google Scholar]
  14. Miller R. J. Multiple calcium channels and neuronal function. Science. 1987 Jan 2;235(4784):46–52. doi: 10.1126/science.2432656. [DOI] [PubMed] [Google Scholar]
  15. Ng S. C., de la Monte S. M., Conboy G. L., Karns L. R., Fishman M. C. Cloning of human GAP-43: growth association and ischemic resurgence. Neuron. 1988 Apr;1(2):133–139. doi: 10.1016/0896-6273(88)90197-3. [DOI] [PubMed] [Google Scholar]
  16. Saper C. B., Standaert D. G., Currie M. G., Schwartz D., Geller D. M., Needleman P. Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas. Science. 1985 Mar 1;227(4690):1047–1049. doi: 10.1126/science.2858127. [DOI] [PubMed] [Google Scholar]
  17. Shinmi O., Kimura S., Yoshizawa T., Sawamura T., Uchiyama Y., Sugita Y., Kanazawa I., Yanagisawa M., Goto K., Masaki T. Presence of endothelin-1 in porcine spinal cord: isolation and sequence determination. Biochem Biophys Res Commun. 1989 Jul 14;162(1):340–346. doi: 10.1016/0006-291x(89)92001-9. [DOI] [PubMed] [Google Scholar]
  18. Simonson M. S., Wann S., Mené P., Dubyak G. R., Kester M., Nakazato Y., Sedor J. R., Dunn M. J. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest. 1989 Feb;83(2):708–712. doi: 10.1172/JCI113935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takuwa N., Takuwa Y., Yanagisawa M., Yamashita K., Masaki T. A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem. 1989 May 15;264(14):7856–7861. [PubMed] [Google Scholar]
  20. 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]
  21. Yoshizawa T., Kimura S., Kanazawa I., Yanagisawa M., Masaki T. Endothelin-1 depolarizes a ventral root potential in the newborn rat spinal cord. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S216–S217. doi: 10.1097/00005344-198900135-00063. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES