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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''ADCYAP1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. PACAP 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 residue (chemistry), residues that belongs to a Secretin family, glu ...

. 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 th ...

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 t ...

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 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 ...

and subsequently increases the

cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

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 Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

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 secon ...

. In addition, it plays a role in

paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...

and

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with ...

regulation of certain types of cells. This gene has five

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s. Exons 1 and 2 encode the

5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly Upstream and downstream (DNA), upstream from the initiation codon. This region is im ...

and

signal peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16–30 amino acids long) present at the ...

, respectively; exon 4 encodes an adenylate cyclase-activating polypeptide 1-related peptide; and exon 5 encodes the mature peptide and

3' UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation (biology), translation termination codon. The 3′-UTR often contains regulatory regions that P ...

. 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 disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(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 Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC1, is a protein that in humans is encoded by the ''ADCYAP1R1'' gene. This receptor binds pituitary adenylate cyclase activating peptide. Function PAC1 is a ...

) in PTSD. In mouse model of heavy alcohol drinking, PACAP seems to mediate alcohol effects on

bed nucleus of the stria terminalis The stria terminalis (or terminal stria) is a structure in the brain consisting of a band of fibers running along the lateral margin of the ventricular surface of the thalamus. Serving as a major output pathway of the amygdala, the stria termina ...

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 complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

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 Professor of Neurology at the University of Copenhagen and Senior Consultant of Neurology at Copenhagen University Hospital - Rigsho ...

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. Formerly known as Alder Biopharmaceuticals, it specializes in therapeutic monoclonal antibodies Monoclonal antibodies (mAbs) have varied t ...

'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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

secretin receptor The secretin receptor is a protein that in humans is encoded by the SCTR gene. This protein is a G protein-coupled receptor which binds secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the enviro ...

References

External links

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

Function

Headache Disorders

Interactions

See also

References

Further reading

External links