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Gene Review

ADM  -  adrenomedullin

Homo sapiens

Synonyms: AM, PAMP
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Disease relevance of ADM


Psychiatry related information on ADM


High impact information on ADM

  • This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM) [10].
  • In Section II of this paper we give a comprehensive review both of tissues and cell lines secreting adrenomedullin and of the mechanisms regulating gene expression [11].
  • In Section III the pharmacology and biochemistry of adrenomedullin binding sites, both specific sites and calcitonin gene-related peptide (CGRP) receptors, are discussed [11].
  • In Section IV the various actions of adrenomedullin are discussed: its actions on cellular growth, the cardiovascular system, the central nervous system, and the endocrine system are all considered [11].
  • The calcitonin family of peptides comprises calcitonin, amylin, two calcitonin gene-related peptides (CGRPs), and adrenomedullin [12].

Chemical compound and disease context of ADM


Biological context of ADM


Anatomical context of ADM

  • In concordance, increased messenger RNA (mRNA) levels of VEGF and ADM were found at culturing macrophages in hypoxia [1].
  • In human trigeminal ganglia, mRNA for ADM and the two CGRP1 receptors was systematically present [21].
  • Adipocyte transcriptional activity, glycerol release, and insulin-mediated glucose transport were studied after exogenous CGRP and ADM exposure [22].
  • In summary, CGRP and ADM are two differentially regulated novel adipose tissue secretion factors exerting autocrine/paracrine roles [22].
  • Depletion of calcium stores in the endoplasmic reticulum (ER) with 1 microM cyclopiazonic acid or 150 nM thapsigargin, or inhibition of ryanodine-sensitive receptors in the ER with 10 microM ryanodine attenuated the ADM-induced NO release [23].

Associations of ADM with chemical compounds

  • These results, taken together with our previous findings that ADM is an angiogenic factor which is upregulated by the nonsteroidal antiestrogen tamoxifen (TAM) in endometrial cells, implicate this peptide as a promoter of tumour growth and a possible target for anticancer strategies [17].
  • Further, the ability of CGRP and ADM to activate adenylate cyclase in cerebromicrovascular and astroglial cell cultures was determined, and the receptors involved were characterized pharmacologically [21].
  • We used a nitrite assay to demonstrate that ADM (10 pM to 100 nM) stimulated NO release from the cells, with a maximal response observed with 1 nM at 30 min [23].
  • No relationship was observed between ADM and left ventricular mass index, aldosterone and creatinine [18].
  • NO responses to ADM were mimicked by 1 mM dibutyryl cAMP, a cAMP analog, and were abrogated by 5 microM H-89, a protein kinase A inhibitor [23].

Physical interactions of ADM


Regulatory relationships of ADM


Other interactions of ADM


Analytical, diagnostic and therapeutic context of ADM

  • METHODS AND RESULTS: Stimulation of HSCs with ADM resulted in a dose-dependent raise in cAMP concentration (radioimmunoassay) and markedly blunted the endothelin-induced increase in [Ca2+]i and cell contraction, as assessed in cells loaded with fura-2 using a morphometric method [35].
  • Specific mRNA for ADM (RT-PCR and Northern blot) was detected in HSCs and increased after incubation of cells with cytokines [35].
  • METHODS: Circulating ADM and its relationship with parameters of cardiovascular hemodynamics, humoral factors and renal function were determined in normal subjects and Htx early (1, 2, 4, 8, 15 and 30 days) and late (32 +/- 16 months) after transplantation [18].
  • Such an increase likely results from renal impairment associated with volume regulation abnormalities, suggesting a potential role for ADM in volume regulation after liver transplantation [4].
  • OBJECTIVES: Circulating adrenomedullin (ADM), a potent vasorelaxing and natriuretic peptide involved in cardiovascular homeostasis, is increased after cardiac and renal transplantation [4].


  1. Hypoxia is an inducer of vasodilator agents in peritoneal macrophages of cirrhotic patients. Cejudo-Martín, P., Morales-Ruiz, M., Ros, J., Navasa, M., Fernández-Varo, G., Fuster, J., Rivera, F., Arroyo, V., Rodés, J., Jiménez, W. Hepatology (2002) [Pubmed]
  2. Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. Ali, N., Yousufzai, S.Y., Abdel-Latif, A.A. Cell. Signal. (2000) [Pubmed]
  3. Association study of calcitonin-receptor-like receptor gene in essential hypertension. Sano, M., Kuroi, N., Nakayama, T., Sato, N., Izumi, Y., Soma, M., Kokubun, S. Am. J. Hypertens. (2005) [Pubmed]
  4. Circulating adrenomedullin is increased in relation with increased creatinine and atrial natriuretic peptide in liver-transplant recipients. Geny, B., Ellero, B., Charloux, A., Brandenberger, G., Doutreleau, S., Piquard, F. Regul. Pept. (2003) [Pubmed]
  5. Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells. Xu, Q., Ohara, N., Chen, W., Liu, J., Sasaki, H., Morikawa, A., Sitruk-Ware, R., Johansson, E.D., Maruo, T. Hum. Reprod. (2006) [Pubmed]
  6. Elevated adrenomedullin mRNA in lymphoblastoid cells from schizophrenic patients. Huang, C.H., Chen, M.L., Tsai, Y.L., Tsai, M.T., Chen, C.H. Neuroreport (2004) [Pubmed]
  7. Adrenomedullin expression in pathogen-challenged oral epithelial cells. Kapas, S., Bansal, A., Bhargava, V., Maher, R., Malli, D., Hagi-Pavli, E., Allaker, R.P. Peptides (2001) [Pubmed]
  8. Relaxation effects of adrenomedullin in isolated rabbit corpus cavernosum smooth muscle. Gokce, G., Bagcivan, I., Kilicarslan, H., Yildirim, S., Gultekin, Y.E., Sarioglu, Y. BJU international. (2004) [Pubmed]
  9. Adrenomedullin and nitrite levels in children with primary nocturnal enuresis. Balat, A., Cekmen, M., Yürekli, M., Gül, A.K., Ozbek, E., Korkut, M., Tarakçioglu, M., Sahinöz, S., Anarat, A. Pediatr. Nephrol. (2002) [Pubmed]
  10. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Brain, S.D., Grant, A.D. Physiol. Rev. (2004) [Pubmed]
  11. Adrenomedullin, a multifunctional regulatory peptide. Hinson, J.P., Kapas, S., Smith, D.M. Endocr. Rev. (2000) [Pubmed]
  12. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Poyner, D.R., Sexton, P.M., Marshall, I., Smith, D.M., Quirion, R., Born, W., Muff, R., Fischer, J.A., Foord, S.M. Pharmacol. Rev. (2002) [Pubmed]
  13. Expression and function of adrenomedullin and its receptors in Conn's adenoma cells. Forneris, M., Gottardo, L., Albertin, G., Malendowicz, L.K., Nussdorfer, G.G. Int. J. Mol. Med. (2001) [Pubmed]
  14. Hypoxic Induction of Receptor Activity-Modifying Protein 2 Alters Regulation of Pulmonary Endothelin-1 by Adrenomedullin: Induction under Normoxia Versus Inhibition under Hypoxia. Dschietzig, T., Richter, C., Asswad, L., Baumann, G., Stangl, K. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  15. Adrenomedullin and calcitonin gene-related peptide interact with the same receptor in cultured human neuroblastoma SK-N-MC cells. Zimmermann, U., Fischer, J.A., Muff, R. Peptides (1995) [Pubmed]
  16. Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis. Laoag-Fernandez, J.B., Maruo, T., Pakarinen, P., Spitz, I.M., Johansson, E. Hum. Reprod. (2003) [Pubmed]
  17. Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth. Oehler, M.K., Norbury, C., Hague, S., Rees, M.C., Bicknell, R. Oncogene (2001) [Pubmed]
  18. Circulating adrenomedullin is increased after heart transplantation. Geny, B., Brandenberger, G., Lonsdorfer, J., Chakfé, N., Haberey, P., Piquard, F. Cardiovasc. Res. (1999) [Pubmed]
  19. Adrenomedullin enhances invasion by trophoblast cell lines. Zhang, X., Green, K.E., Yallampalli, C., Dong, Y.L. Biol. Reprod. (2005) [Pubmed]
  20. Interaction of human adrenomedullin 13-52 with calcitonin gene-related peptide receptors in the microvasculature of the rat and hamster. Hall, J.M., Siney, L., Lippton, H., Hyman, A., Kang-Chang, J., Brain, S.D. Br. J. Pharmacol. (1995) [Pubmed]
  21. Functional calcitonin gene-related peptide type 1 and adrenomedullin receptors in human trigeminal ganglia, brain vessels, and cerebromicrovascular or astroglial cells in culture. Moreno, M.J., Cohen, Z., Stanimirovic, D.B., Hamel, E. J. Cereb. Blood Flow Metab. (1999) [Pubmed]
  22. Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Linscheid, P., Seboek, D., Zulewski, H., Keller, U., Müller, B. Endocrinology (2005) [Pubmed]
  23. Adrenomedullin stimulates nitric oxide release from SK-N-SH human neuroblastoma cells by modulating intracellular calcium mobilization. Xu, Y., Krukoff, T.L. Endocrinology (2005) [Pubmed]
  24. The seven amino acids of human RAMP2 (86) and RAMP3 (59) are critical for agonist binding to human adrenomedullin receptors. Kuwasako, K., Kitamura, K., Ito, K., Uemura, T., Yanagita, Y., Kato, J., Sakata, T., Eto, T. J. Biol. Chem. (2001) [Pubmed]
  25. Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners. Pio, R., Martinez, A., Unsworth, E.J., Kowalak, J.A., Bengoechea, J.A., Zipfel, P.F., Elsasser, T.H., Cuttitta, F. J. Biol. Chem. (2001) [Pubmed]
  26. Adrenomedullin is expressed in pancreatic cancer and stimulates cell proliferation and invasion in an autocrine manner via the adrenomedullin receptor, ADMR. Ramachandran, V., Arumugam, T., Hwang, R.F., Greenson, J.K., Simeone, D.M., Logsdon, C.D. Cancer Res. (2007) [Pubmed]
  27. The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin. Hasbak, P., Eskesen, K., Lind, H., Holst, J., Edvinsson, L. Basic & clinical pharmacology & toxicology. (2006) [Pubmed]
  28. Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo. Shibata, Y., Kashiwagi, B., Arai, S., Magari, T., Suzuki, K., Honma, S. Urology (2006) [Pubmed]
  29. Adrenomedullin is decreased in preeclampsia because of failed response to epidermal growth factor and impaired syncytialization. Li, H., Dakour, J., Kaufman, S., Guilbert, L.J., Winkler-Lowen, B., Morrish, D.W. Hypertension (2003) [Pubmed]
  30. Adrenomedullin regulates cellular glutathione content via modulation of gamma-glutamate-cysteine ligase catalytic subunit expression. Kim, J.Y., Yim, J.H., Cho, J.H., Kim, J.H., Ko, J.H., Kim, S.M., Park, S., Park, J.H. Endocrinology (2006) [Pubmed]
  31. The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. Kamitani, S., Asakawa, M., Shimekake, Y., Kuwasako, K., Nakahara, K., Sakata, T. FEBS Lett. (1999) [Pubmed]
  32. Sequencing of a calcitonin receptor-like receptor in salmon Oncorhynchus gorbuscha. Functional studies using the human receptor activity-modifying proteins. Pidoux, E., Cressent, M. Gene (2002) [Pubmed]
  33. Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. Kuwasako, K., Kitamura, K., Nagoshi, Y., Eto, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  34. Post-transcriptional regulation of CRLR expression during hypoxia. Cueille, C., Birot, O., Bigard, X., Hagner, S., Garel, J.M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  35. Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility. Görbig, M.N., Ginès, P., Bataller, R., Nicolás, J.M., Garcia-Ramallo, E., Cejudo, P., Sancho-Bru, P., Jiménez, W., Arroyo, V., Rodés, J. J. Hepatol. (2001) [Pubmed]
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