Plasma adrenomedullin levels in patients with migraine during natural attack and attack free period

Yıl 2016, Cilt: 3 Sayı: 4, 153 - 8, 15.04.2016

Aylin Akcali Sirma Geyik Ilker Dogru Arzu Dogru Muhittin Yurekli Abdurrahman Neyal Ayse Balat Munife Neyal

Öz

Objective: The role of Calcitonin G related peptide (CGRP) in migraine has been demonsrated. The aim of this study was to examine the role of Adrenomedullin (AM) which is a member of the calcitonin/CGRP/amylin family in migraine patients during naturel attack and attack free period.

Material and Methods: 26 migraine patients (11 with aura, 15 without aura) and 26 healty participants were involved. Blood samples were obtained from each patient in attack and attack free period, then compared with each other and control group.

Results: Mean plasma AM levels were 18.95 pmol/L during migraine attacks, 26.01 pmol/L between attacks, and 33.38 pmol/L in the control group. AM levels of migraine patients were significantly lower than controls during non-attack periods (p=0.001) and more interestingly, it further decreased during attack periods (p=0.001). A comparison of the mean plasma AM levels of migraine with and without aura cases revealed the same statistically significant difference (p=0.00).

Conclusion: The persistently low AM levels in migraine patients gave the impression that in physiological conditions there may be a balance between CGRP and AM and this may be changed towards to the site of CGRP in migraine pathophysiology while causing a decline in AM levels as we had found. Further studies regarding on AM involvement in migraine pathophysiology are needed to confirm these results. 

 

Anahtar Kelimeler

Adrenomedullin; Calcitonin; CGRP; Amylin; Headache; Migraine; Pathophysiology

Medical Science and Discovery

Öz

Kaynakça

• Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990, 28(2):183-87.
• Kis B, Abraham CS, Deli MA, Kobayashi H, Wada A, Niwa M, Yamashita H, Ueta Y. Adrenomedullin in the cerebral circulation. Peptides 2001, 22(11):1825-1834.
• Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002, 22(1):54-61.
• Walker CS, Hay DL. CGRP in the trigeminovascular system: a role for CGRP, adrenomedullin and amylin receptors? Br J Pharmacol, 170(7):1293-307.
• Kruuse C, Frandsen E, Schifter S, Thomsen L L, Birk S, Olesen J. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache. Cephalalgia, 2004. 24(7): 547-53.
• Petersen KA, Birk S, Kitamura K, Olesen J. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders. Cephalalgia 2009, 29(1):23-30.
• Friberg L, Olesen J, Olsen TS, Karle A, Ekman R, Fahrenkrug J. Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura. Cephalalgia 1994, 14(1):47-54.
• Tfelt-Hansen P, Le H. Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review. J Headache Pain 2009, 10(3):137-43.
• Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 1993, 192(2):553-60.
• Kis B, Deli MA, Kobayashi H, Abraham CS, Yanagita T, Kaiya H, Isse T, Nishi R, Gotoh S, Kangawa K et al. Adrenomedullin regulates blood-brain barrier functions in vitro. Neuroreport 2001, 12(18):4139-42.
• Kis B, Kaiya H, Nishi R, Deli MA, Abraham CS, Yanagita T, Isse T, Gotoh S, Kobayashi H, Wada A et al. Cerebral endothelial cells are a major source of adrenomedullin. J Neuroendocrinol 2002, 14(4):283-93.
• Bela K, Csongor AS, Deli MA, Ueta Y. Adrenomedullin and migraine. Headache 2002, 42(10):1064-65.
• Kis B, Abraham CS, Deli MA, Kobayashi H, Niwa M, Yamashita H, Busija DW, Ueta Y. Adrenomedullin, an autocrine mediator of blood-brain barrier function. Hypertens Res 2003, 26 Suppl:S61-70.
• Petersen KA, Birk S, Kitamura K, Olesen J. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders. Cephalalgia 2009, 29(1):23-30.
• The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004, 24 Suppl 1:9-160.
• Rognant, N., Bacchetta J, Juillard L. [Comparison of methods estimating a quantitative parameter: evaluation of the agreement]. Nephrol Ther. 9(2): 92-7.
• McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998, 393(6683):333-9.
• Honda M, Nakagawa S, Hayashi K, Kitagawa N, Tsutsumi K, Nagata I, Niwa M. Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5. Cell Mol Neurobiol, 2006. 26(2):109-18.
• Ladoux, A. C. Frelin. Coordinated Up-regulation by hypoxia of adrenomedullin and one of its putative receptors (RDC-1) in cells of the rat blood-brain barrier. J Biol Chem, 2000. 275(51):39914-9.
• Sams A, Knyihar-Csillik E, Engberg J, Szok D, Tajti J, Bodi I, Edvinsson L, Vecsei L, Jansen-Olesen I. CGRP and adrenomedullin receptor populations in human cerebral arteries: in vitro pharmacological and molecular investigations in different artery sizes. Eur J Pharmacol 2000, 408(2):183-93.
• Kobari M, Fukuuchi Y, Tomita M, Tanahashi N, Takeda H, Yokoyama M. Calcitonin gene-related peptide (CGRP) and the regulation of cerebral parenchymal vessels. Brain Res 1995, 698(1-2):95-9.
• McCulloch J, Uddman R, Kingman TA, Edvinsson L. Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci U S A 1986, 83(15):5731-35.
• Nikitenko LL, Blucher N, Fox SB, Bicknell R, Smith DM, Rees MC. Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms. J Cell Sci 2006, 119(Pt 5):910-22.
• Akiyama S, Kawasaki H, Shimogai A, Kurosaki Y. Adrenomedullin inhibits neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in rat mesenteric resistance arteries. Peptides 2001, 22(11):1887-93.
• Akiyama S, Hatanaka Y, Hobara N, Honghua J, Kosugi K, Takayama F, Kawasaki H. Effect of adrenomedullin on adrenergic vasoconstriction in mesenteric resistance arteries of the rat. J Pharmacol Sci 2005, 99(3):264-71.
• Ishimitsu T, Nishikimi T, Saito Y, Kitamura K, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H. Plasma levels of adrenomedullin, a newly identified hypotensive peptide, in patients with hypertension and renal failure. J Clin Invest 1994, 94(5):2158-61.
• Kato J, Kitamura K, Uemura T, Kuwasako K, Kita T, Kangawa K, Eto T. Plasma levels of adrenomedullin and atrial and brain natriuretic peptides in the general population: their relations to age and pulse pressure. Hypertens Res 2002, 25(6):887-92.
• Kawano S, Kawagoe Y, Kuwasako K, Shimamoto S, Igarashi K, Tokashiki M, Kitamura K, Kato J. Gender-related alterations in plasma adrenomedullin level and its correlation with body weight gain. Endocr Connect 2015, 4(1):43-9.