Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''ADCYAP1''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
pituitary adenylate cyclase-activating polypeptide is similar to
vasoactive intestinal peptide
Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the lig ...
. One of its effects is to stimulate
enterochromaffin-like cell
Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell found in the gastric glands of the gastric mucosa beneath the epithelium, in particular in the vicinity of parietal cells, that aid in the production of gastric acid via t ...
s. It binds to
vasoactive intestinal peptide receptor and to the
pituitary adenylate cyclase-activating polypeptide receptor.
Function
This gene encodes adenylate cyclase-activating polypeptide 1. Mediated by adenylate cyclase-activating polypeptide 1 receptors, this polypeptide stimulates adenylate cyclase and subsequently increases the cAMP level in target cells. Adenylate cyclase-activating polypeptide 1 not only is a hypophysiotropic hormone (i.e. a substance that induces activity in the
hypophysis), but also functions as a
neurotransmitter and
neuromodulator
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
. In addition, it plays a role in paracrine and autocrine regulation of certain types of cells. This gene is composed of five exons. Exons 1 and 2 encode the 5' UTR and signal peptide, respectively; exon 4 encodes an adenylate cyclase-activating polypeptide 1-related peptide; and exon 5 encodes the mature peptide and 3' UTR. This gene encodes three different mature peptides, including two isotypes: a shorter form and a longer form.
A version of this gene has been associated with
post-traumatic stress disorder
Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...
(PTSD) in women (but not men).
This disorder involves a maladaptive psychological response to traumatic, i.e. existence-threatening, events. Ressler et al. identified an association of a SNP in the gene coding for pituitary adenylate cyclase-activating polypeptide (PACAP), implicating this peptide and its receptor (PAC1) in PTSD.
Headache Disorders
Both isoforms of pituitary adenylate cyclase-activating polypeptide (pituitary adenylate cyclase-activating polypeptide-38 and pituitary adenylate cyclase-activating polypeptide-27) have been implicated in
migraine pathogenesis.
A Danish research group led by Dr.
Messoud Ashina
Messoud Ashina (born December 29, 1965) is a Danish-Azerbaijani neurologist and neuroscientist. He is currently a Professor of Neurology at the University of Copenhagen and leads the Human Migraine Research Unit at the Danish Headache Center, ...
found that intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 induced migraine attacks in 58% of people with migraine,
whilst the corresponding migraine induction rate was 55% for pituitary adenylate cyclase-activating polypeptide-27.
Treatments with monoclonal antibodies have been investigated to target pituitary adenylate cyclase-activating polypeptide or its receptors for the treatment of primary headache disorders.
Alder BioPharmaceuticals
Lundbeck Seattle Biopharmaceuticals is a pharmaceutical development company based in Bothell, Washington
Bothell () is a city in King County, Washington, King and Snohomish County, Washington, Snohomish counties in the U.S. state of Washingto ...
's ALD1910, which targets the peptide, began a phase I study in October 2019.
Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.
Interactions
Pituitary adenylate cyclase-activating peptide has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
secretin receptor
Human secretin receptor (gene name SCTR) is a G protein-coupled receptor which binds secretin and is the leading member (''i.e.'', first cloned) of the class B GPCR subfamily.
Interactions
Secretin receptor has been shown to interact with pitui ...
.
See also
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Adenylate cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction:
:A ...
*
Pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
References
Further reading
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External links
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PACAP receptor peptides
{{Growth factor receptor modulators
Genes on human chromosome 18