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Neurotherapeutics
Erschienen in: Neurotherapeutics 2/2018

01.04.2018 | Review

Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine

verfasst von: Anne Luise Haulund Vollesen, Faisal Mohammad Amin, Messoud Ashina

Erschienen in: Neurotherapeutics | Ausgabe 2/2018

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Abstract

Here, we review the role of pituitary adenylate cyclase-activating peptide-38 (PACAP38) in migraine pathophysiology and data implicating PAC1 receptor as a future drug target in migraine. Much remains to be fully elucidated about migraine pathophysiology, but recent attention has focused on signaling molecule PACAP38, a vasodilator able to induce migraine attacks in patients who experience migraine without aura. PACAP38, with marked and sustained effect, dilates extracerebral arteries but not the middle cerebral artery. The selective affinity of PACAP38 to the PAC1 receptor makes this receptor a highly interesting and potential novel target for migraine treatment. Efficacy of antagonism of this receptor should be investigated in randomized clinical trials.
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Literatur
1.
Miyata A, Jiang L, Dahl RD, et al. Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun 1990; 170: 643–648.
2.
Schytz HW, Birk S, Wienecke T, et al. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 2009; 132: 16–25.
3.
Schytz HW, Schoonman GG, Ashina M. What have we learnt from triggering migraine? Curr Opin Neurol 2010; 23: 259–65.
4.
Kaiser E a., Russo AF. CGRP and migraine: Could PACAP play a role too? Neuropeptides 2013; 47: 451–461.
5.
6.
Vaudry D, Gonzalez BJ, Basille M, et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol Rev 2000; 52: 269–324.
7.
Vécsei L, Tuka B, Tajti J. Role of PACAP in migraine headaches. Brain 2014; 137: 650–651.
8.
Banks WA, Kastin A, Komaki G, et al. Passage of pituary adenylate cyclase activating polypeptide1-27 and pituary adenylate cyclase activating polypeptide1-38 across the blood-brain barrier. J Pharmacol Exp Ther 1993; 267: 690–696.
9.
Gulbenkian S, Uddman R, Edvinsson L. Neuronal messengers in the human cerebral circulation. Peptides 2001; 22: 995–1007.
10.
Edvinsson L, Uddman R. Neurobiology in primary headaches. Brain Res Rev 2005; 48: 438–456.
11.
Tajti J, Uddman R, Moller S, et al. Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst 1999; 76: 176–183.CrossRefPubMed
12.
Uddman R, Tajti J, Moller S, et al. Neuronal messengers and peptide receptors in the human sphenopalatine and otic ganglia. Brain Res 1999; 826: 193–199.
13.
Mikkelsen JD, Hannibal J, Larsen PJ, et al. Pituitary adenylate cyclase activating peptide (PACAP) mRNA in the rat neocortex. Neurosci Lett 1994; 171: 121–124.
14.
Koves K, Arimura A, Somogyvari-Vigh A, et al. Immunohistochemical demonstration of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, in the ovine hypothalamus. Endocrinology 1990; 127: 264–271.
15.
Vigh S, Arimura A, Koves K, et al. Immunohistochemical localization of the neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), in human and primate hypothalamus. Peptides 1991; 12: 313–318.
16.
Kivipelto L, Absood A, Arimura A, et al. The distribution of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity is distinct from helodermin- and helospectin-like immunoreactivities in the rat brain. J Chem Neuroanat 1992; 5: 85–94.
17.
Tamada Y, Tanaka M, Ichitani Y, et al. Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive neuronal elements in rat hypothalamus and median eminence with special reference to morphological background of its effect on anterior pituitary--light and electron microscopic. Neurosci Lett 1994; 180: 105–108.
18.
Hannibal J, Mikkelsen JD, Fahrenkrug J, et al. Pituitary adenylate cyclase-activating peptide gene expression in corticotropin-releasing factor-containing parvicellular neurons of the rat hypothalamic paraventricular nucleus is induced by colchicine, but not by adrenalectomy, acute osmotic, ether, or restraint stress. Endocrinology 1995; 136: 4116–4124.
19.
Hannibal J, Mikkelsen JD, Clausen H, et al. Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus. Regul Pept 1995; 55: 133–148.
20.
Mikkelsen JD, Hannibal J, Fahrenkrug J, et al. Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP related peptide (PRP) in the rat median eminence and pituitary. J Neuroendocrinol 1995; 7: 47–55.
21.
Moller K, Zhang YZ, Hakanson R, et al. Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. Neuroscience 1993; 57: 725–732.
22.
Mulder H, Uddman R, Moller K, et al. Pituitary adenylate cyclase activating polypeptide expression in sensory neurons. Neuroscience 1994; 63: 307–312.
23.
Dun NJ, Miyazaki T, Tang H, et al. Pituitary adenylate cyclase activating polypeptide immunoreactivity in the rat spinal cord and medulla: implication of sensory and autonomic functions. Neuroscience 1996; 73: 677–686.
24.
Masuo Y, Suzuki N, Matsumoto H, et al. Regional distribution of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat central nervous system as determined by sandwich-enzyme immunoassay. Brain Res 1993; 602: 57–63.
25.
Takahashi K, Totsune K, Murakami O, et al. Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity in human hypothalamus: co-localization with arginine vasopressin. Regul Pept 1994; 50: 267–275.
26.
Palkovits M, Somogyvari-Vigh A, Arimura A. Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain nuclei. Brain Res 1995; 699: 116–120.
27.
Hannibal J. Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study. J Comp Neurol 2002; 453: 389–417.
28.
Nonaka N, Farr SA, Nakamachi T, et al. Intranasal administration of PACAP: uptake by brain and regional brain targeting with cyclodextrins. Peptides 2012; 36: 168–175.
29.
Das M, Vihlen CS, Legradi G. Hypothalamic and brainstem sources of pituitary adenylate cyclase-activating polypeptide nerve fibers innervating the hypothalamic paraventricular nucleus in the rat. J Comp Neurol 2007; 500: 761–776.
30.
Ghatei M a, Takahashi K, Suzuki Y, et al. Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissues. J Endocrinol 1993; 136: 159–166.
31.
Nielsen HS, Hannibal J, Fahrenkrug J. Expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the postnatal and adult rat cerebellar cortex. Neuroreport 1998; 9: 2639–2642.
32.
Tajti J, Uddman R, Edvinsson L. Neuropeptide localization in the ‘migraine generator’ region of the human brainstem. Cephalalgia 2001; 21: 96–101.
33.
Farnham MMJ, Li Q, Goodchild AK, et al. PACAP is expressed in sympathoexcitatory bulbospinal C1 neurons of the brain stem and increases sympathetic nerve activity in vivo. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1304-R1311.
34.
Uddman R, Tajti J, Hou M, et al. Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2. Cephalalgia; 22: 112–116.
35.
Ødum L, Petersen LJ, Skov PS, et al. Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in human dermal neurons and causes histamine release from skin mast cells. Inflamm Res 1998; 47: 488–492.
36.
Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 2012; 166: 4–17.
37.
Dickson L, Finlayson K. Pharmacology & Therapeutics VPAC and PAC receptors: from ligands to function. Pharmacol Ther 2009; 121: 294–316.
38.
Knutsson M, Edvinsson L. Distribution of mRNA for VIP and PACAP receptors in human cerebral arteries and cranial ganglia. Neuroreport 2002; 13: 507–509.
39.
Hashimoto H, Nogi H, Mori K, et al. Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol 1996; 371: 567–577.
40.
Shioda S, Shuto Y, Somogyvari-Vigh A, et al. Localization and gene expression of the receptor for pituitary adenylate cyclase-activating polypeptide in the rat brain. Neurosci Res 1997; 28: 345–354.
41.
Usdin TB, Bonner TI, Mezey E. Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology 1994; 135: 2662–2680.
42.
Chaudhary P, Baumann TK. Expression of VPAC2 receptor and PAC1 receptor splice variants in the trigeminal ganglion of the adult rat. Brain Res Mol Brain Res 2002; 104: 137–142.
43.
Nogi H, Hashimoto H, Hagihara N, et al. Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP receptor, vasoactive intestinal polypeptide (VIP), and VIP receptors in the rat superior cervical ganglion. Neurosci Lett 1997; 227: 37–40.
44.
Brandenburg CA, May V, Braas KM. Identification of endogenous sympathetic neuron pituitary adenylate cyclase-activating polypeptide (PACAP): depolarization regulates production and secretion through induction of multiple propeptide transcripts. J Neurosci 1997; 17: 4045–4055.
45.
Zhou CJ, Kikuyama S, Shibanuma M, et al. Cellular distribution of the splice variants of the receptor for pituitary adenylate cyclase-activating polypeptide (PAC(1)-R) in the rat brain by in situ RT-PCR. Brain Res Mol Brain Res 2000; 75: 150–158.
46.
Basille M, Vaudry D, Coulouarn Y, et al. Comparative distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites and PACAP receptor mRNAs in the rat brain during development. J Comp Neurol 2000; 425: 495–509.
47.
Baun M, Hay-Schmidt A, Edvinsson L, et al. Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat. Eur J Pharmacol 2011; 670: 186–194.
48.
Chan KY, Baun M, De Vries R, et al. Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery. Cephalalgia 2011; 31: 181–9.
49.
May V, Parsons RL. G protein-coupled receptor endosomal signaling and regulation of neuronal excitability and stress responses: signaling options and lessons from the PAC1 receptor. J Cell Physiol 2017; 232: 698–706.
50.
Ashina M, Hansen JM, Olesen J. Pearls and pitfalls in human pharmacological models of migraine: 30 years’ experience. Cephalalgia 2013; 33: 540–553.
51.
Amin FM, Hougaard A, Magon S, et al. Change in brain network connectivity during PACAP38-induced migraine attacks: a resting-state functional MRI study. Neurology 2016; 86: 180–187.
52.
Amin FM, Hougaard A, Schytz HW, et al. Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain 2014; 137: 779–794.
53.
Birk S, Sitarz JT, Petersen KA, et al. The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers. Regul Pept 2007; 140: 185–191.
54.
Vollesen ALH, Guo S, Ashina M. PACAP38 dose-response pilot study in migraine patients. Cephalalgia 2016; 0: 1–5.
55.
Amin FM, Asghar MS, Guo S, et al. Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers. Cephalalgia 2012; 32: 140–149.
56.
Amin FM, Asghar MS, Hougaard A, et al. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol 2013; 12: 454–461.
57.
Boni L, Ploug K, Olesen J, et al. The in vivo effect of VIP, PACAP-38 and PACAP-27 and mRNA expression of their receptors in rat middle meningeal artery. Cephalalgia 2009; 29: 837–847.
58.
Akerman S, Goadsby PJ. Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: relevance to migraine. Sci Transl Med 2015; 7: 308ra157.
59.
Baun M, Pedersen MHF, Olesen J, et al. Dural mast cell degranulation is a putative mechanism for headache induced by PACAP-38. Cephalalgia 2012; 32: 337–45.
60.
Bhatt DK, Gupta S, Olesen J, et al. PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat: possible involvement of mast cells. Cephalalgia 2014; 34: 877–886.
61.
Seeley WW, Menon V, Schatzberg AF, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007; 27: 2349–2356.
62.
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 1–38.
63.
Farmer MA, Baliki MN, Apkarian AV. A dynamic network perspective of chronic pain. Neurosci Lett 2012; 520: 197–203.
64.
Lindquist KA, Wager TD, Kober H, et al. The brain basis of emotion: a meta-analytic review. Behav Brain Sci 2012; 35: 121–143.
65.
Sava SL, de Pasqua V, Magis D, et al. Effects of visual cortex activation on the nociceptive blink reflex in healthy subjects. PLOS ONE 2014; 9: e100198.
66.
Peyron R, Laurent B, García-Larrea L. Functional imaging of brain responses to pain. a review and meta-analysis (2000). Neurophysiol Clin Neurophysiol 2000; 30: 263–288.
67.
Guo S, Vollesen ALH, Hansen RD, et al. Part I: pituitary adenylate cyclase-activating polypeptide-38 induced migraine-like attacks in patients with and without familial aggregation of migraine. Cephalalgia 2017; 37: 125–135.CrossRefPubMed
68.
Flavell SW, Kim TK, Gray JM, et al. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron 2008; 60: 1022–1038.
69.
Tuka B, Helyes Z, Markovics A, et al. Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients. Cephalalgia 2013; 33: 1085–95.
70.
Zagami AS, Edvinsson L, Goadsby PJ. Pituitary adenylate cyclase activating polypeptide and migraine. Ann Clin Transl Neurol 2014; 1(12): 1036–40.
71.
Riesco N, Cernuda-Morollón E, Pascual J. Neuropeptides as a marker for chronic headache. Curr Pain Headache Rep 2017;21:18.CrossRefPubMed
72.
Han X, Dong Z, Hou L, et al. Interictal plasma pituitary adenylate cyclase-activating polypeptide levels are decreased in migraineurs but remain unchanged in patients with tension-type headache. Clin Chim Acta 2015; 450: 151–154.
73.
Cernuda-Morollón E, Riesco N, Martínez-Camblor P, et al. No change in interictal PACAP Levels in peripheral blood in women with chronic migraine. Headache 2016; 56: 1448–1454.
74.
Han X, Ran Y, Su M, et al. Chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in rats. Mol Pain 2017; 13:1–10.
75.
Rahmann A, Wienecke T, Hansen JM, et al. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 2008; 28: 226–236.
76.
Sághy E, Payrits M, Helyes ZS, et al. Stimulatory effect of pituitary adenylate cyclase-activating polypeptide 6-38, M65 and vasoactive intestinal polypeptide 6-28 on trigeminal sensory neurons. Neuroscience 2015; 308: 144–156.
77.
Jansen-Olesen I, Baun M, Amrutkar D V, et al. PACAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor. Neuropeptides 2014; 48: 53–64.
78.
Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016; 15: 382–390.
79.
Bigal ME, Edvinsson L, Rapoport AM, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol 2015; 14: 1091–1100.
80.
Dodick DW, Goadsby PJ, Spierings ELH, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014; 13: 885–892.
81.
Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache J Head Face Pain 2017; 57: 47–55.
82.
83.
Metadaten
Titel
Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine
verfasst von
Anne Luise Haulund Vollesen
Faisal Mohammad Amin
Messoud Ashina
Publikationsdatum
01.04.2018
Verlag
Springer International Publishing
Erschienen in
Neurotherapeutics / Ausgabe 2/2018
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-017-0596-x

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