Dataset Information

Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.

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.

SUBMITTER: Vollesen ALH

PROVIDER: S-EPMC5935633 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.

Vollesen Anne Luise Haulund ALH Amin Faisal Mohammad FM Ashina Messoud M

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20180401 2

Here, we review the role of pituitary adenylate cyclase-activating peptide-38 (PACAP38) in migraine pathophysiology and data implicating PAC<sub>1</sub> 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 ...[more]

PMID: 29464574

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Project description:Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-conserved neuropeptide characteristic of vertebrates. This pluripotent hypothalamic neuropeptide regulates neurotransmitter release, intestinal motility, metabolism, cell division/differentiation, and immunity. In vertebrates, PACAP has a specific receptor (PAC1) but it can also activate the Vasoactive Intestinal Peptide receptors (VPAC1 and VPAC2). The evolution of the vertebrate PACAP ligand - receptor pair has been well-described. In contrast, the situation in invertebrates is much less clear. The PACAP ligand - receptor pair in invertebrates has mainly been studied using heterologous antibodies raised against mammalian peptides. A few partial PACAP cDNA clones sharing >87% aa identity with vertebrate PACAP have been isolated from a cnidarian, several protostomes and tunicates but no gene has been reported. Moreover, current evolutionary models of the peptide and receptors using molecular data from phylogenetically distinct invertebrate species (mostly nematodes and arthropods) suggests the PACAP ligand and receptors are exclusive to vertebrate genomes. A basal deuterostome, the cephalochordate amphioxus (Branchiostoma floridae), is the only invertebrate in which elements of a PACAP-like system exists but the peptides and receptor share relatively low sequence conservation with the vertebrate homolog system and are a hybrid with the vertebrate glucagon system. In this study, the evolution of the PACAP system is revisited taking advantage of the burgeoning sequence data (genome and transcriptomes) available for invertebrates to uncover clues about when it first appeared. The results suggest that elements of the PACAP system are absent from protozoans, non-bilaterians, and protostomes and they only emerged after the protostome-deuterostome divergence. PACAP and its receptors appeared in vertebrate genomes and they probably shared a common ancestral origin with the cephalochordate PACAP/GCG-like system which after the genome tetraploidization events that preceded the vertebrate radiation generated the PACAP ligand and receptor pair and also the other members of the Secretin family peptides and their receptors.

Dataset Information

Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.

Publications

Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.

Similar Datasets

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