Pituitary adenylate cyclase-activating peptide

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Adenylate cyclase activating polypeptide 1 (pituitary)
Protein ADCYAP1 PDB 2d2p.png
PDB rendering based on 2d2p.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM102980 MGI105094 HomoloGene869 ChEMBL: 5692 GeneCards: ADCYAP1 Gene
RNA expression pattern
PBB GE ADCYAP1 206281 at tn.png
More reference expression data
Species Human Mouse
Entrez 116 11516
Ensembl ENSG00000141433 ENSMUSG00000024256
UniProt P18509 O70176
RefSeq (mRNA) NM_001099733 NM_009625
RefSeq (protein) NP_001093203 NP_033755
Location (UCSC) Chr 18:
0.9 – 0.91 Mb
Chr 17:
93.2 – 93.21 Mb
PubMed search [1] [2]

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


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.[2]

Recently 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.


Pituitary adenylate cyclase-activating peptide has been shown to interact with Secretin receptor.[4]

See also[edit]


  1. ^ 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. 
  2. ^ a b "Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary)". 
  3. ^ 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. doi:10.1038/nature09856. PMC 3046811. PMID 21350482. 
  4. ^ 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. ISSN 0002-9513. PMID 1335692. 

Further reading[edit]

  • Conconi MT, Spinazzi R, Nussdorfer GG (2006). "Endogenous ligands of PACAP/VIP receptors in the autocrine-paracrine regulation of the adrenal gland.". Int. Rev. Cytol. 249: 1–51. doi:10.1016/S0074-7696(06)49001-X. PMID 16697281. 
  • Cross SH, Charlton JA, Nan X, Bird AP (1994). "Purification of CpG islands using a methylated DNA binding column.". Nat. Genet. 6 (3): 236–44. doi:10.1038/ng0394-236. PMID 8012384. 
  • Dautzenberg FM, Mevenkamp G, Wille S, Hauger RL (2000). "N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants.". J. Neuroendocrinol. 11 (12): 941–9. doi:10.1046/j.1365-2826.1999.00411.x. PMID 10583729. 
  • Fahrenkrug J (2002). "Gut/brain peptides in the genital tract: VIP and PACAP.". Scand. J. Clin. Lab. Invest. Suppl. 234: 35–9. PMID 11713978. 
  • Fahrenkrug J (2006). "PACAP--a multifacetted neuropeptide.". Chronobiol. Int. 23 (1-2): 53–61. doi:10.1080/07420520500464569. PMID 16687279. 
  • Felley CP, Qian JM, Mantey S et al. (1993). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release.". Am. J. Physiol. 263 (6 Pt 1): G901–7. PMID 1335692. 
  • Geng L, Ju G (2000). "[The discovery of pituitary adenylate cyclase activating polypeptide (PACAP) and its research progress]". Sheng li ke xue jin zhan [Progress in physiology] 28 (1): 29–34. PMID 10921074. 
  • Gourlet P, Vandermeers A, Robberecht P, Deschodt-Lanckman M (1997). "Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP-27, but not PACAP-38) degradation by the neutral endopeptidase EC". Biochem. Pharmacol. 54 (4): 509–15. doi:10.1016/S0006-2952(97)00207-4. PMID 9313778. 
  • Inagaki N, Yoshida H, Mizuta M et al. (1994). "Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells.". Proc. Natl. Acad. Sci. U.S.A. 91 (7): 2679–83. doi:10.1073/pnas.91.7.2679. PMC 43433. PMID 8146174. 
  • Inooka H, Endo S, Kitada C et al. (1993). "Pituitary adenylate cyclase activating polypeptide (PACAP) with 27 residues. Conformation determined by 1H NMR and CD spectroscopies and distance geometry in 25% methanol solution.". Int. J. Pept. Protein Res. 40 (5): 456–64. doi:10.1111/j.1399-3011.1992.tb00324.x. PMID 1483839. 
  • Kimura C, Ohkubo S, Ogi K et al. (1990). "A novel peptide which stimulates adenylate cyclase: molecular cloning and characterization of the ovine and human cDNAs.". Biochem. Biophys. Res. Commun. 166 (1): 81–9. doi:10.1016/0006-291X(90)91914-E. PMID 2302217. 
  • Nakata M, Yada T (2007). "PACAP in the glucose and energy homeostasis: physiological role and therapeutic potential.". Curr. Pharm. Des. 13 (11): 1105–12. doi:10.2174/138161207780618948. PMID 17430174. 
  • Ohkubo S, Kimura C, Ogi K et al. (1992). "Primary structure and characterization of the precursor to human pituitary adenylate cyclase activating polypeptide.". DNA Cell Biol. 11 (1): 21–30. doi:10.1089/dna.1992.11.21. PMID 1739432. 
  • Ohtaki T, Masuda Y, Ishibashi Y et al. (1994). "Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide.". J. Biol. Chem. 268 (35): 26650–7. PMID 8253796. 
  • Pérez-Jurado LA, Francke U (1993). "Dinucleotide repeat polymorphism at the human pituitary adenylate cyclase activating polypeptide (PACAP) gene.". Hum. Mol. Genet. 2 (6): 827. doi:10.1093/hmg/2.6.827-a. PMID 8353512. 
  • Waschek JA (2002). "Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration.". Dev. Neurosci. 24 (1): 14–23. doi:10.1159/000064942. PMID 12145407. 
  • Weber B, Riess O, Daneshvar H et al. (1993). "(CA)n-dinucleotide repeat at the PDEB locus in 4p16.3.". Hum. Mol. Genet. 2 (6): 827. doi:10.1093/hmg/2.6.827. PMID 8394765. 
  • Wray V, Kakoschke C, Nokihara K, Naruse S (1993). "Solution structure of pituitary adenylate cyclase activating polypeptide by nuclear magnetic resonance spectroscopy.". Biochemistry 32 (22): 5832–41. doi:10.1021/bi00073a016. PMID 8504103. 
  • Zeng N, Athmann C, Kang T et al. (1999). "PACAP type I receptor activation regulates ECL cells and gastric acid secretion.". J. Clin. Invest. 104 (10): 1383–91. doi:10.1172/JCI7537. PMC 409843. PMID 10562300. 

External links[edit]

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