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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 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[]


  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.
  2. 2.0 2.1 Entrez Gene: ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary).
  3. K. J. Ressler, K. B. Mercer, B. Bradley, T. Jovanovic, A. Mahan, K. Kerley, S. D. Norrholm, V. Kilaru, A. K. Smith, A. J. Myers, M. Ramirez, A. Engel, S. E. Hammack, D. Toufexis, K. M. Braas, E. B. Binder and V. May. (2011). Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature, 470, 492-7
  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. 263 (6 Pt 1): G901–7.

Further reading[]

  • 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.
  • 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.
  • 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.
  • Fahrenkrug J (2002). Gut/brain peptides in the genital tract: VIP and PACAP.. Scand. J. Clin. Lab. Invest. Suppl. 234: 35–9.
  • Fahrenkrug J (2006). PACAP--a multifacetted neuropeptide.. Chronobiol. Int. 23 (1-2): 53–61.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Nakata M, Yada T (2007). PACAP in the glucose and energy homeostasis: physiological role and therapeutic potential.. Curr. Pharm. Des. 13 (11): 1105–12.
  • 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.
  • 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.
  • 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.
  • Waschek JA (2002). Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration.. Dev. Neurosci. 24 (1): 14–23.
  • 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.
  • 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.
  • 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.

External links[]

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

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