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 There are two known receptors for the vasoactive intestinal peptide (VIP) termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) to some degree. Both receptors are members of the 7 tra ...

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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

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 Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

pathogenesis. A Danish research group led by Dr. Messoud Ashina 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, doing business as, 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 trai ...

with secretin receptor.

References

External links

*
PACAP receptor peptides
{{Growth factor receptor modulators Genes on human chromosome 18

Function

Headache Disorders

Interactions

See also

References

Further reading

External links