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Pituitary adenylate cyclase-activating polypeptide receptors in the trigeminovascular system: implications for migraine.

ABSTRACT: The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in a wide range of functions including vasodilatation, neuroprotection, nociception and neurogenic inflammation. PACAP activates three distinct receptors, the PAC1 receptor, which responds to PACAP, and the VPAC1 and VPAC2 receptors, which respond to both PACAP and vasoactive intestinal polypeptide. The trigeminovascular system plays a key role in migraine and contains the trigeminal nerve, which is the major conduit of craniofacial pain. PACAP is expressed throughout the trigeminovascular system and in higher brain regions involved in processing pain. Evidence from human clinical studies suggests that PACAP may act outside the blood-brain barrier in the pathogenesis of migraine. However, the precise mechanisms involved remain unclear. PACAP potentially induces migraine attacks by activating different receptors in different cell types and tissues. This complexity prompted this review of PACAP receptor pharmacology, expression and function in the trigeminovascular system. Current evidence suggests that the PAC1 receptor is the likely pathophysiological target of PACAP in migraine. However, multiple PACAP receptors are expressed in key parts of the trigeminovascular system and further work is required to determine their contribution to PACAP physiology and the pathology of migraine. LINKED ARTICLES:This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.

SUBMITTER: Sundrum T

PROVIDER: S-EPMC6177619 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Pituitary adenylate cyclase-activating polypeptide receptors in the trigeminovascular system: implications for migraine.

Sundrum Tahlia T Walker Christopher S CS

British journal of pharmacology 20171025 21

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in a wide range of functions including vasodilatation, neuroprotection, nociception and neurogenic inflammation. PACAP activates three distinct receptors, the PAC1 receptor, which responds to PACAP, and the VPAC1 and VPAC2 receptors, which respond to both PACAP and vasoactive intestinal polypeptide. The trigeminovascular system plays a key role in migraine and contains ...[more]

PMID: 28977676

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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

Pituitary adenylate cyclase-activating polypeptide receptors in the trigeminovascular system: implications for migraine.

Publications

Pituitary adenylate cyclase-activating polypeptide receptors in the trigeminovascular system: implications for migraine.

Similar Datasets

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