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. One of its effects is to stimulate
enterochromaffin-like cells. 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
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. 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 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. 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) in PTSD. In mouse model of heavy alcohol drinking, PACAP seems to mediate alcohol effects on
bed nucleus of the stria terminalis.
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 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's ALD1910, which targets the peptide, began a phase I study in October 2019.
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 with
secretin receptor.
See also
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Adenylate cyclase
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Pituitary gland
The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
References
Further reading
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External links
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{{Growth factor receptor modulators
Genes on human chromosome 18