Pituitary adenylate cyclase-activating peptide

Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene.[5][6] 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 PACAP receptor.

ADCYAP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesADCYAP1, PACAP, adenylate cyclase activating polypeptide 1
External IDsOMIM: 102980 MGI: 105094 HomoloGene: 869 GeneCards: ADCYAP1
Gene location (Human)
Chr.Chromosome 18 (human)[1]
Band18p11.32Start904,871 bp[1]
End912,172 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

116

11516

Ensembl

ENSG00000141433

ENSMUSG00000024256

UniProt

P18509

O70176

RefSeq (mRNA)

NM_001099733
NM_001117

NM_009625
NM_001315503
NM_001315504

RefSeq (protein)

NP_001093203
NP_001108

NP_001302432
NP_001302433
NP_033755

Location (UCSC)Chr 18: 0.9 – 0.91 MbChr 17: 93.2 – 93.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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. 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.[6]

A version of this gene has been associated with post-traumatic stress disorder (PTSD) in women (but not men).[7] 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

Research has shown that administration of intravenous PACAP-38 (two species of PACAP have been identified, one that is 38 amino acids long and one that is 27 amino acids long) triggers delayed "migraine-like headaches" in most subjects who experience migraine headaches.[8] Treatments with monoclonal antibodies are being developed targeting PACAP or its receptors for the treatment of primary headache disorders. These include: AMG‐301 developed by Amgen Inc., which targets the PAC1 receptor and has completed phase II trials; and ALD1910, developed by Alder BioPharmaceuticals, which targets the peptide and began a phase I study in October 2019.[9][10]

Interactions

Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor.[11]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000141433 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000024256 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hosoya M, Kimura C, Ogi K, Ohkubo S, Miyamoto Y, Kugoh H, Shimizu M, Onda H, Oshimura M, Arimura A, et al. (Feb 1992). "Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene". Biochim Biophys Acta. 1129 (2): 199–206. doi:10.1016/0167-4781(92)90488-l. PMID 1730060.
  6. "Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)".
  7. Ressler, KJ; Mercer, KB; Bradley, B; Jovanovic, T; Mahan, A; Kerley, K; Norrholm, SD; Kilaru, V; Smith, AK; Myers, AJ; Ramirez, M; Engel, A; Hammack, SE; Toufexis, D; Braas, KM; Binder, EB; May, V (Feb 24, 2011). "Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor". Nature. 470 (7335): 492–7. Bibcode:2011Natur.470..492R. doi:10.1038/nature09856. PMC 3046811. PMID 21350482.
  8. Waschek, James A.; Baca, Serapio M.; Akerman, Simon (2018). "PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma". The Journal of Headache and Pain. 19 (1): 23. doi:10.1186/s10194-018-0850-6. ISSN 1129-2369. PMC 5849772. PMID 29536279.
  9. Bertels, Zachariah; Pradhan, Amynah Amir Ali (2019). "Emerging Treatment Targets for Migraine and Other Headaches". Headache: The Journal of Head and Face Pain. 59 (S2): 50–65. doi:10.1111/head.13585. ISSN 0017-8748. PMC 6986366. PMID 31291018.
  10. "Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine". GlobeNewswire. 10 October 2019. Retrieved 10 October 2019.
  11. Felley, C P; Qian J M; Mantey S; Pradhan T; Jensen R T (Dec 1992). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release". Am. J. Physiol. UNITED STATES. 263 (6 Pt 1): G901–7. doi:10.1152/ajpgi.1992.263.6.G901. ISSN 0002-9513. PMID 1335692.

Further reading

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