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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Aug;82(2):538–543. doi: 10.1172/JCI113629

Calcitonin gene-related peptide is a stimulator of renin secretion.

A Kurtz 1, R Muff 1, W Born 1, J M Lundberg 1, B I Millberg 1, M P Gnädinger 1, D E Uehlinger 1, P Weidmann 1, T Hökfelt 1, J A Fischer 1
PMCID: PMC303545  PMID: 2841355

Abstract

Calcitonin gene-related peptide (CGRP) was found to stimulate renin secretion in vivo in normal human volunteers. Moreover, CGRP stimulated the release of renin in vitro from isolated rat renal juxtaglomerular cells (half-maximal effective concentration [EC50] 100 nM) concomitant with stimulation of cAMP production (EC50 60 nM). Immunoreactive CGRP was recognized in rat renal cortical nerve fibers, and intact rat CGRP was identified in extracts of the rat renal cortex. Because CGRP containing sensory nerve fibers are seen in the region of the juxtaglomerular apparatus, it would seem that the release of CGRP from these afferent nerves may be involved in the physiological control of renin secretion.

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Selected References

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  1. Amara S. G., Jonas V., Rosenfeld M. G., Ong E. S., Evans R. M. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 1982 Jul 15;298(5871):240–244. doi: 10.1038/298240a0. [DOI] [PubMed] [Google Scholar]
  2. Brain S. D., Williams T. J., Tippins J. R., Morris H. R., MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature. 1985 Jan 3;313(5997):54–56. doi: 10.1038/313054a0. [DOI] [PubMed] [Google Scholar]
  3. Churchill P. C. Second messengers in renin secretion. Am J Physiol. 1985 Aug;249(2 Pt 2):F175–F184. doi: 10.1152/ajprenal.1985.249.2.F175. [DOI] [PubMed] [Google Scholar]
  4. Davis J. O., Freeman R. H. Mechanisms regulating renin release. Physiol Rev. 1976 Jan;56(1):1–56. doi: 10.1152/physrev.1976.56.1.1. [DOI] [PubMed] [Google Scholar]
  5. Edvinsson L., Fredholm B. B., Hamel E., Jansen I., Verrecchia C. Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat. Neurosci Lett. 1985 Jul 31;58(2):213–217. doi: 10.1016/0304-3940(85)90166-1. [DOI] [PubMed] [Google Scholar]
  6. Fischer J. A., Born W. Novel peptides from the calcitonin gene: expression, receptors and biological function. Peptides. 1985;6 (Suppl 3):265–271. doi: 10.1016/0196-9781(85)90384-5. [DOI] [PubMed] [Google Scholar]
  7. Fischer J. A., Tobler P. H., Kaufmann M., Born W., Henke H., Cooper P. E., Sagar S. M., Martin J. B. Calcitonin: regional distribution of the hormone and its binding sites in the human brain and pituitary. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7801–7805. doi: 10.1073/pnas.78.12.7801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Franco-Cereceda A., Gennari C., Nami R., Agnusdei D., Pernow J., Lundberg J. M., Fischer J. A. Cardiovascular effects of calcitonin gene-related peptides I and II in man. Circ Res. 1987 Mar;60(3):393–397. doi: 10.1161/01.res.60.3.393. [DOI] [PubMed] [Google Scholar]
  9. Franco-Cereceda A., Henke H., Lundberg J. M., Petermann J. B., Hökfelt T., Fischer J. A. Calcitonin gene-related peptide (CGRP) in capsaicin-sensitive substance P-immunoreactive sensory neurons in animals and man: distribution and release by capsaicin. Peptides. 1987 Mar-Apr;8(2):399–410. doi: 10.1016/0196-9781(87)90117-3. [DOI] [PubMed] [Google Scholar]
  10. Gennari C., Fischer J. A. Cardiovascular action of calcitonin gene-related peptide in humans. Calcif Tissue Int. 1985 Dec;37(6):581–584. doi: 10.1007/BF02554909. [DOI] [PubMed] [Google Scholar]
  11. Girgis S. I., Macdonald D. W., Stevenson J. C., Bevis P. J., Lynch C., Wimalawansa S. J., Self C. H., Morris H. R., MacIntyre I. Calcitonin gene-related peptide: potent vasodilator and major product of calcitonin gene. Lancet. 1985 Jul 6;2(8445):14–16. doi: 10.1016/s0140-6736(85)90059-5. [DOI] [PubMed] [Google Scholar]
  12. Hackenthal E., Taugner R. Hormonal signals and intracellular messengers for renin secretion. Mol Cell Endocrinol. 1986 Sep;47(1-2):1–12. doi: 10.1016/0303-7207(86)90010-9. [DOI] [PubMed] [Google Scholar]
  13. Hall J. E., Granger J. P. Renal hemodynamic actions of angiotensin II: interaction with tubuloglomerular feedback. Am J Physiol. 1983 Aug;245(2):R166–R173. doi: 10.1152/ajpregu.1983.245.2.R166. [DOI] [PubMed] [Google Scholar]
  14. Kubota M., Moseley J. M., Butera L., Dusting G. J., MacDonald P. S., Martin T. J. Calcitonin gene-related peptide stimulates cyclic AMP formation in rat aortic smooth muscle cells. Biochem Biophys Res Commun. 1985 Oct 15;132(1):88–94. doi: 10.1016/0006-291x(85)90992-1. [DOI] [PubMed] [Google Scholar]
  15. Kurtz A., Della Bruna R., Pfeilschifter J., Taugner R., Bauer C. Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4769–4773. doi: 10.1073/pnas.83.13.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurtz A., Pfeilschifter J., Hutter A., Bührle C., Nobiling R., Taugner R., Hackenthal E., Bauer C. Role of protein kinase C in inhibition of renin release caused by vasoconstrictors. Am J Physiol. 1986 Apr;250(4 Pt 1):C563–C571. doi: 10.1152/ajpcell.1986.250.4.C563. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Malatino L. S., Fiore C. E., Foti R., Guzzardi F., Tamburino G. Acute effects of salmon calcitonin in man include stimulation of the renin-angiotensin-aldosterone system. Miner Electrolyte Metab. 1987;13(5):316–322. [PubMed] [Google Scholar]
  19. Mason R. T., Peterfreund R. A., Sawchenko P. E., Corrigan A. Z., Rivier J. E., Vale W. W. Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells. Nature. 1984 Apr 12;308(5960):653–655. doi: 10.1038/308653a0. [DOI] [PubMed] [Google Scholar]
  20. Mason R. T., Shulkes A., Zajac J. D., Fletcher A. E., Hardy K. J., Martin T. J. Basal and stimulated release of calcitonin gene-related peptide (CGRP) in patients with medullary thyroid carcinoma. Clin Endocrinol (Oxf) 1986 Dec;25(6):675–685. doi: 10.1111/j.1365-2265.1986.tb03623.x. [DOI] [PubMed] [Google Scholar]
  21. Morris H. R., Panico M., Etienne T., Tippins J., Girgis S. I., MacIntyre I. Isolation and characterization of human calcitonin gene-related peptide. Nature. 1984 Apr 19;308(5961):746–748. doi: 10.1038/308746a0. [DOI] [PubMed] [Google Scholar]
  22. Petermann J. B., Born W., Chang J. Y., Fischer J. A. Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord. J Biol Chem. 1987 Jan 15;262(2):542–545. [PubMed] [Google Scholar]
  23. Roos B. A., Fischer J. A., Pignat W., Alander C. B., Raisz L. G. Evaluation of the in vivo and in vitro calcium-regulating actions of noncalcitonin peptides produced via calcitonin gene expression. Endocrinology. 1986 Jan;118(1):46–51. doi: 10.1210/endo-118-1-46. [DOI] [PubMed] [Google Scholar]
  24. Rosenfeld M. G., Mermod J. J., Amara S. G., Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W., Evans R. M. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature. 1983 Jul 14;304(5922):129–135. doi: 10.1038/304129a0. [DOI] [PubMed] [Google Scholar]
  25. Saria A., Gamse R., Petermann J., Fischer J. A., Theodorsson-Norheim E., Lundberg J. M. Simultaneous release of several tachykinins and calcitonin gene-related peptide from rat spinal cord slices. Neurosci Lett. 1986 Jan 30;63(3):310–314. doi: 10.1016/0304-3940(86)90376-9. [DOI] [PubMed] [Google Scholar]
  26. Sealey J. E., Gerten-Banes J., Laragh J. H. The renin system: Variations in man measured by radioimmunoassay or bioassay. Kidney Int. 1972 Apr;1(4):240–253. doi: 10.1038/ki.1972.34. [DOI] [PubMed] [Google Scholar]
  27. Sigrist S., Franco-Cereceda A., Muff R., Henke H., Lundberg J. M., Fischer J. A. Specific receptor and cardiovascular effects of calcitonin gene-related peptide. Endocrinology. 1986 Jul;119(1):381–389. doi: 10.1210/endo-119-1-381. [DOI] [PubMed] [Google Scholar]
  28. Steenbergh P. H., Höppener J. W., Zandberg J., Visser A., Lips C. J., Jansz H. S. Structure and expression of the human calcitonin/CGRP genes. FEBS Lett. 1986 Dec 1;209(1):97–103. doi: 10.1016/0014-5793(86)81091-2. [DOI] [PubMed] [Google Scholar]
  29. Struthers A. D., Brown M. J., Macdonald D. W., Beacham J. L., Stevenson J. C., Morris H. R., MacIntyre I. Human calcitonin gene related peptide: a potent endogenous vasodilator in man. Clin Sci (Lond) 1986 Apr;70(4):389–393. doi: 10.1042/cs0700389. [DOI] [PubMed] [Google Scholar]
  30. Tobler P. H., Jöhl A., Born W., Maier R., Fischer J. A. Identity of calcitonin extracted from normal human thyroid glands with synthetic human calcitonin-(1-32). Biochim Biophys Acta. 1982 Sep 22;707(1):59–65. doi: 10.1016/0167-4838(82)90396-x. [DOI] [PubMed] [Google Scholar]
  31. Tschopp F. A., Tobler P. H., Fischer J. A. Calcitonin gene-related peptide in the human thyroid, pituitary and brain. Mol Cell Endocrinol. 1984 Jun;36(1-2):53–57. doi: 10.1016/0303-7207(84)90084-4. [DOI] [PubMed] [Google Scholar]

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