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] pituitary adenylate cyclase-activating polypeptide 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.

ADCYAP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesADCYAP1, PACAP, adenylate cyclase activating polypeptide 1
External IDsOMIM: 102980 MGI: 105094 HomoloGene: 869 GeneCards: ADCYAP1
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: 93.51 – 93.51 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

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.[8][9] 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,[8] whilst the corresponding migraine induction rate was 55% for pituitary adenylate cyclase-activating polypeptide-27.[9] 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.[10][11] Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.[12]

Interactions

Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor.[13]

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, et al. (January 1992). "Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 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, et al. (February 2011). "Post-traumatic stress disorder is associated with pituitary adenylate cyclase-activating polypeptide and the PAC1 receptor". Nature. 470 (7335): 492–7. Bibcode:2011Natur.470..492R. doi:10.1038/nature09856. PMC 3046811. PMID 21350482.
  8. Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M (January 2009). "pituitary adenylate cyclase-activating polypeptide-38 induces migraine-like attacks in patients with migraine without aura". Brain. 132 (Pt 1): 16–25. doi:10.1093/brain/awn307. PMID 19052139.
  9. Ghanizada H, Al-Karagholi MA, Arngrim N, Olesen J, Ashina M (January 2020). "PACAP27 induces migraine-like attacks in migraine patients". Cephalalgia. 40 (1): 57–67. doi:10.1177/0333102419864507. PMID 31299857. S2CID 196349669.
  10. Bertels Z, Pradhan AA (July 2019). "Emerging Treatment Targets for Migraine and Other Headaches". Headache. 59 Suppl 2 (S2): 50–65. doi:10.1111/head.13585. PMC 6986366. PMID 31291018.
  11. "Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine". Globenewswire News Room. GlobeNewswire. 10 October 2019. Retrieved 10 October 2019.
  12. Ashina M, Doležil D, Bonner JH, Zhou L, Klatt J, Picard H, Mikol DD (January 2021). "A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention". Cephalalgia. 41 (1): 33–44. doi:10.1177/0333102420970889. PMC 7786389. PMID 33231489.
  13. Felley CP, Qian JM, Mantey S, Pradhan T, Jensen RT (December 1992). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release". The American Journal of Physiology. 263 (6 Pt 1): G901-7. doi:10.1152/ajpgi.1992.263.6.G901. PMID 1335692.

Further reading

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