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Gene Review

ADCYAP1  -  adenylate cyclase activating polypeptide 1...

Homo sapiens

Synonyms: PACAP, Pituitary adenylate cyclase-activating polypeptide
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Disease relevance of ADCYAP1

  • The growth rate of rodent embryonic neuroblasts and human neuroblastoma cell lines is regulated in part by autocrine or paracrine actions of neuropeptides of the family that includes vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), and pituitary adenylate cyclase-activating peptide (PACAP) [1].
  • Reduction in the activity of PMNs to respond to PACAP was observed after cell exposure to inhibitors of the cAMP/protein kinase A, protein kinase C, and PI3K pathways, to pertussis toxin, genistein, and after chelation of intracellular calcium or after extracellular calcium depletion [2].
  • These data demonstrate the presence in human Y-79 retinoblastoma cells of specific PACAP receptors and provide further evidence that PACAP may act as a neurotransmitter/neuromodulator in mammalian retina [3].
  • Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors [4].
  • Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis [5].

Psychiatry related information on ADCYAP1

  • The patients suffer from severe mental retardation and have a bleeding tendency with mild thrombocytopenia, and their fibroblasts show increased PACAP mRNA levels [6].
  • Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) both regulate multiple neuroendocrine functions and feeding behavior [7].
  • Recent evidence indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) might play an important role in rapid eye movement sleep (REMS) generation at the pontine level in rats [8].
  • This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population [9].
  • However, after castration, PACAP led only to a slight amelioration of the behavioral symptoms [10].

High impact information on ADCYAP1

  • The pituitary adenylate cyclase-activating polypeptide (PACAP)/ glucagon superfamily includes nine hormones in humans that are related by structure, distribution (especially the brain and gut), function (often by activation of cAMP), and receptors (a subset of seven-transmembrane receptors) [11].
  • The diverse functions of PACAP include regulation of proliferation, differentiation, and apoptosis in some cell populations [11].
  • In addition, PACAP regulates metabolism and the cardiovascular, endocrine, and immune systems, although the physiological event(s) that coordinates PACAP responses remains to be identified [11].
  • Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland [12].
  • This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types [13].

Chemical compound and disease context of ADCYAP1


Biological context of ADCYAP1

  • The ADCYAP1 gene is located on chromosome 18p11 linked to type 2 diabetes [17].
  • The G allele frequencies of g.9863G>A (G54D) and g.12712C>G of the ADCYAP1 gene were higher in type 2 diabetic patients than in non-diabetic control subjects (21.0% vs 15.8%, P=0.04; 5.3% vs 3.0%, P=0.045) [17].
  • Two novel SNPs, g.9863G>A (G54D) in exon 3 and g.12712C>G in the 3'-UTR of exon 5 of the ADCYAP1 gene (accession number X60435), were found [17].
  • Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes [17].
  • Dinucleotide repeat polymorphism at the human pituitary adenylate cyclase activating polypeptide (PACAP) gene [18].

Anatomical context of ADCYAP1


Associations of ADCYAP1 with chemical compounds


Physical interactions of ADCYAP1

  • In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland [24].
  • A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after PACAP stimulation and in primary cultured hippocampal neurons [25].

Enzymatic interactions of ADCYAP1


Co-localisations of ADCYAP1

  • 7. The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve structures within the human cavernous tissue, and that the peptides are effective relaxants of CC preparations in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
  • PACAP was found to be co-localized with ChAT in nerve fibers of the intraganglionic spiral bundle and beneath the inner and outer hair cells within the organ of Corti [28].
  • PACAP and melanopsin were colocalized in the RGCs and PACAP-containing nerve fibers, seemingly innervating the retinorecipient part of the SCN [29].

Regulatory relationships of ADCYAP1


Other interactions of ADCYAP1

  • Since NF-kappaB represents a focal point for various stimuli and induces the expression of many proinflammatory genes, its targeting by VIP and PACAP positions them as important anti-inflammatory agents [19].
  • Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta [35].
  • Pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined by real-time RT-PCR [36].
  • Both PACAP and NGF have pro-inflammatory activities on monocytes [21].
  • However, neither in tissues nor cell lines did PACAP mRNA expression correlate with TH mRNA expression [37].

Analytical, diagnostic and therapeutic context of ADCYAP1


  1. Differential effects of peptide histidine isoleucine (PHI) and related peptides on stimulation and suppression of neuroblastoma cell proliferation. A novel VIP-independent action of PHI via MAP kinase. Lelièvre, V., Pineau, N., Du, J., Wen, C.H., Nguyen, T., Janet, T., Muller, J.M., Waschek, J.A. J. Biol. Chem. (1998) [Pubmed]
  2. Differential calcium regulation of proinflammatory activities in human neutrophils exposed to the neuropeptide pituitary adenylate cyclase-activating protein. Harfi, I., Corazza, F., D'Hondt, S., Sariban, E. J. Immunol. (2005) [Pubmed]
  3. Presence of pituitary adenylate cyclase-activating polypeptide receptors in Y-79 human retinoblastoma cells. Olianas, M.C., Ennas, M.G., Lampis, G., Onali, P. J. Neurochem. (1996) [Pubmed]
  4. Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors. Juarranz, M.G., Bolaños, O., Gutiérrez-Cañas, I., Lerner, E.A., Robberecht, P., Carmena, M.J., Prieto, J.C., Rodríguez-Henche, N. Cell. Signal. (2001) [Pubmed]
  5. Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis. Isobe, K., Tatsuno, I., Yashiro, T., Nanmoku, T., Takekoshi, K., Kawakami, Y., Nakai, T. Regul. Pept. (2003) [Pubmed]
  6. The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. Freson, K., Hashimoto, H., Thys, C., Wittevrongel, C., Danloy, S., Morita, Y., Shintani, N., Tomiyama, Y., Vermylen, J., Hoylaerts, M.F., Baba, A., Van Geet, C. J. Clin. Invest. (2004) [Pubmed]
  7. Pituitary adenylate cyclase-activating polypeptide directly modulates the activity of proopiomelanocortin neurons in the rat arcuate nucleus. Mounien, L., Bizet, P., Boutelet, I., Gourcerol, G., Fournier, A., Vaudry, H., J??gou, S. Neuroscience (2006) [Pubmed]
  8. Immunocytochemical distribution of VIP and PACAP in the rat brain stem: implications for REM sleep physiology. Ahnaou, A., Yon, L., Arluison, M., Vaudry, H., Hannibal, J., Hamon, M., Adrien, J., Bourgin, P. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  9. Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders. Ishiguro, H., Ohtsuki, T., Okubo, Y., Kurumaji, A., Arinami, T. Journal of neural transmission (Vienna, Austria : 1996) (2001) [Pubmed]
  10. Effect of PACAP in 6-OHDA-induced injury of the substantia nigra in intact young and ovariectomized female rats. Reglödi, D., Lubics, A., Kiss, P., Lengvári, I., Gaszner, B., Tóth, G., Hegyi, O., Tamás, A. Neuropeptides (2006) [Pubmed]
  11. The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Sherwood, N.M., Krueckl, S.L., McRory, J.E. Endocr. Rev. (2000) [Pubmed]
  12. Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland. Rawlings, S.R., Hezareh, M. Endocr. Rev. (1996) [Pubmed]
  13. Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Vaudry, D., Gonzalez, B.J., Basille, M., Yon, L., Fournier, A., Vaudry, H. Pharmacol. Rev. (2000) [Pubmed]
  14. Pituitary adenylate cyclase-activating polypeptide type I receptors mediate cyclic AMP-dependent enhancement of neuronal acetylcholine sensitivity. Margiotta, J.F., Pardi, D. Mol. Pharmacol. (1995) [Pubmed]
  15. Pituitary adenylate cyclase activating peptide (PACAP) immunoreactivity in the ureter of the duck. Mirabella, N., Squillacioti, C., Germano, G., Varricchio, E., Paino, G. Cell Tissue Res. (2001) [Pubmed]
  16. Retinoic acid regulation of the VIP and PACAP autocrine ligand and receptor system in human neuroblastoma cell lines. Waschek, J.A., Lelievre, V., Bravo, D.T., Nguyen, T., Muller, J.M. Peptides (1997) [Pubmed]
  17. Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes. Gu, H.F. Hum. Mutat. (2002) [Pubmed]
  18. Dinucleotide repeat polymorphism at the human pituitary adenylate cyclase activating polypeptide (PACAP) gene. Pérez-Jurado, L.A., Francke, U. Hum. Mol. Genet. (1993) [Pubmed]
  19. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit nuclear factor-kappa B-dependent gene activation at multiple levels in the human monocytic cell line THP-1. Delgado, M., Ganea, D. J. Biol. Chem. (2001) [Pubmed]
  20. Regulation of human polymorphonuclear leukocytes functions by the neuropeptide pituitary adenylate cyclase-activating polypeptide after activation of MAPKs. Harfi, I., D'Hondt, S., Corazza, F., Sariban, E. J. Immunol. (2004) [Pubmed]
  21. The neuropeptide pituitary adenylate cyclase activating protein stimulates human monocytes by transactivation of the Trk/NGF pathway. El Zein, N., Badran, B.M., Sariban, E. Cell. Signal. (2007) [Pubmed]
  22. Anorexigenic effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide in the chick brain are mediated by corticotrophin-releasing factor. Tachibana, T., Saito, E.S., Takahashi, H., Saito, S., Tomonaga, S., Boswell, T., Furuse, M. Regul. Pept. (2004) [Pubmed]
  23. Gut/brain peptides in the genital tract: VIP and PACAP. Fahrenkrug, J. Scand. J. Clin. Lab. Invest. Suppl. (2001) [Pubmed]
  24. Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate. Solano, R.M., Carmena, M.J., Carrero, I., Cavallaro, S., Roman, F., Hueso, C., Travali, S., Lopez-Fraile, N., Guijarro, L.G., Prieto, J.C. Endocrinology (1996) [Pubmed]
  25. A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Hattori, T., Baba, K., Matsuzaki, S., Honda, A., Miyoshi, K., Inoue, K., Taniguchi, M., Hashimoto, H., Shintani, N., Baba, A., Shimizu, S., Yukioka, F., Kumamoto, N., Yamaguchi, A., Tohyama, M., Katayama, T. Mol. Psychiatry (2007) [Pubmed]
  26. Two salmon neuropeptides encoded by one brain cDNA are structurally related to members of the glucagon superfamily. Parker, D.B., Coe, I.R., Dixon, G.H., Sherwood, N.M. Eur. J. Biochem. (1993) [Pubmed]
  27. Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive intestinal polypeptide in human corpus cavernosum. Hedlund, P., Alm, P., Ekström, P., Fahrenkrug, J., Hannibal, J., Hedlund, H., Larsson, B., Andersson, K.E. Br. J. Pharmacol. (1995) [Pubmed]
  28. Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea. Drescher, M.J., Drescher, D.G., Khan, K.M., Hatfield, J.S., Ramakrishnan, N.A., Abu-Hamdan, M.D., Lemonnier, L.A. Neuroscience (2006) [Pubmed]
  29. Melanopsin is expressed in PACAP-containing retinal ganglion cells of the human retinohypothalamic tract. Hannibal, J., Hindersson, P., Ostergaard, J., Georg, B., Heegaard, S., Larsen, P.J., Fahrenkrug, J. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  30. Pituitary adenylate cyclase-activating polypeptide stimulates secretion in T84 cells. Nguyen, T.D., Heintz, G.G., Cohn, J.A. Gastroenterology (1992) [Pubmed]
  31. Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on adenohypophyseal Hormone secretion in normal men. Chiodera, P., Volpi, R., Capretti, L., Caffarri, G., Magotti, M.G., Coiro, V. Neuroendocrinology (1996) [Pubmed]
  32. Role of VIP, PACAP, and related peptides in the regulation of the hypothalamo-pituitary-adrenal axis. Nussdorfer, G.G., Malendowicz, L.K. Peptides (1998) [Pubmed]
  33. Neuropeptides in human salivary (submandibular and parotid) glands. Hauser-Kronberger, C., Albegger, K., Saria, A., Hacker, G.W. Acta Otolaryngol. (1992) [Pubmed]
  34. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Arimura, A., Shioda, S. Frontiers in neuroendocrinology. (1995) [Pubmed]
  35. Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta. Scaldaferri, M.L., Modesti, A., Palumbo, C., Ulisse, S., Fabbri, A., Piccione, E., Frajese, G., Moretti, C. Endocrinology (2000) [Pubmed]
  36. Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells. Kidd, M., Modlin, I.M., Eick, G.N., Champaneria, M.C. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  37. Expression of mRNAs for PACAP and its receptor in human neuroblastomas and their relationship to catecholamine synthesis. Isobe, K., Kaneko, M., Kaneko, S., Nissato, S., Nanmoku, T., Takekoshi, K., Okuda, Y., Kawakami, Y. Regul. Pept. (2004) [Pubmed]
  38. PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas. Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets. Portela-Gomes, G.M., Lukinius, A., Ljungberg, O., Efendic, S., Ahrén, B., Abdel-Halim, S.M. Regul. Pept. (2003) [Pubmed]
  39. Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas. Oka, H., Jin, L., Reubi, J.C., Qian, X., Scheithauer, B.W., Fujii, K., Kameya, T., Lloyd, R.V. Am. J. Pathol. (1998) [Pubmed]
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