Biology:Pituitary adenylate cyclase-activating peptide

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 gene.[1][2] 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.

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 has 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.[2]

A version of this gene has been associated with post-traumatic stress disorder (PTSD) in women (but not men).[3] 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.[4]

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.[5][6] 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,[5] whilst the corresponding migraine induction rate was 55% for pituitary adenylate cyclase-activating polypeptide-27.[6] 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.[7][8] Amgen's AMG-301, which targets the PAC1 receptor, failed to show greater efficacy than placebo in phase II trials.[9]

Interactions

Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor.[10]

See also

References

  1. ↑ "Structure of the human pituitary adenylate cyclase activating polypeptide (PACAP) gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1129 (2): 199–206. January 1992. doi:10.1016/0167-4781(92)90488-l. PMID 1730060. 
  2. ↑ 2.0 2.1 "Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=116. 
  3. ↑ "Post-traumatic stress disorder is associated with pituitary adenylate cyclase-activating polypeptide and the PAC1 receptor". Nature 470 (7335): 492–7. February 2011. doi:10.1038/nature09856. PMID 21350482. Bibcode: 2011Natur.470..492R. 
  4. ↑ Lauren Lepeak ... (1 December 2023). "Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) of the Bed Nucleus of the Stria Terminalis Mediates Heavy Alcohol Drinking in Mice". eNeuro. doi:10.1523/ENEURO.0424-23.2023. PMID 38053471. 
  5. ↑ 5.0 5.1 "pituitary adenylate cyclase-activating polypeptide-38 induces migraine-like attacks in patients with migraine without aura". Brain 132 (Pt 1): 16–25. January 2009. doi:10.1093/brain/awn307. PMID 19052139. 
  6. ↑ 6.0 6.1 "PACAP27 induces migraine-like attacks in migraine patients". Cephalalgia 40 (1): 57–67. January 2020. doi:10.1177/0333102419864507. PMID 31299857. 
  7. ↑ "Emerging Treatment Targets for Migraine and Other Headaches". Headache 59 Suppl 2 (S2): 50–65. July 2019. doi:10.1111/head.13585. PMID 31291018. 
  8. ↑ "Alder BioPharmaceuticals® Announces First-in-Human Dosing in Phase 1 ALD1910 Study for Preventive Treatment of Migraine". Globenewswire News Room (GlobeNewswire). 10 October 2019. https://www.globenewswire.com/news-release/2019/10/10/1927997/0/en/Alder-BioPharmaceuticals-Announces-First-in-Human-Dosing-in-Phase-1-ALD1910-Study-for-Preventive-Treatment-of-Migraine.html. 
  9. ↑ "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. January 2021. doi:10.1177/0333102420970889. PMID 33231489. 
  10. ↑ "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. December 1992. doi:10.1152/ajpgi.1992.263.6.G901. PMID 1335692. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Pituitary_adenylate_cyclase-activating_peptide&oldid=3683386"