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Gene Review

Adcyap1r1  -  adenylate cyclase activating polypeptide 1...

Mus musculus

Synonyms: 2900024I10Rik, AI846590, PAC1, PAC1R, PACAP type I receptor, ...
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Disease relevance of Adcyap1r1


Psychiatry related information on Adcyap1r1

  • We clearly demonstrate that mice with a ubiquitous but not with a forebrain-specific deletion of PAC1 exhibit elevated locomotor activity and strongly reduced anxiety-like behavior [6].
  • In contrast, PAC1-deficient mice displayed markedly abnormal social behaviors [7].
  • In aggregate, these results uncover PAC1 signaling as an important factor in the development and/or functioning of neural pathways associated with pheromone processing and the regulation of social interactions in mice [7].

High impact information on Adcyap1r1

  • Thus, these results are consistent with a physiological role for the PAC1 receptor in glucose homeostasis, notably during food intake [8].
  • We show here by in situ hybridization that genes for the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and one of its high-affinity receptors (PAC1) are widely expressed in the mouse neural tube on embryonic day (E) 10 [9].
  • Src family tyrosine kinase inhibitors also inhibited platelet aggregation and decreased the PAC-1 binding caused by costimulation of G(i) and G(z) signaling pathways in aspirin-treated platelets [10].
  • The disintegrin flavorodin and the RGD analogue fradafiban also induce fibrinogen binding, whereas the blocking MoAbs 2G12 and P2 and the activation-specific MoAb PAC-1 do not [11].
  • Transfection analysis of murine PAC-1 promoter-reporter constructs established that in T cells, sequences necessary for basal and induced transcription reside within a 200-bp region located immediately upstream of the transcription initiation sites [12].

Chemical compound and disease context of Adcyap1r1

  • The outside-in signaling of the ectopically expressed alphaIIbbeta3 integrin was studied in B16a murine melanoma cells using a monoclonal antibody, specifically directed to the activated conformation of alphaIIbbeta3, PAC-1 and the physiological ligand, fibrinogen [13].
  • Ligand-mimetic anti-alphaIIb beta3 antibody PAC-1 inhibits tyrosine signaling, proliferation and lung colonization of melanoma cells [14].
  • Furthermore, PAC-1 binding to B16a cells induced a significant decrease in phosphotyrosine-positive melanoma cells within 30 min [14].

Biological context of Adcyap1r1


Anatomical context of Adcyap1r1


Associations of Adcyap1r1 with chemical compounds

  • PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance [8].
  • Here we have used the formalin test, thermal laser stimulation and mechanical von Frey stimulation to investigate possible alteration of PAC1-/- mice nociceptive behaviour [22].
  • To test this hypothesis and to assess the importance of PAC1-signalling in vivo, we analyzed glutamate transporter expression in mice with a PAC1 knockout [23].
  • PAC-1 transcription induced by phorbol myristate acetate stimulation and the expression of the v-ras or v-raf oncogene is mediated via the E-box motif and an AP-2-related site and coincides with increased binding activity of the constitutive 53-kDa E-box-binding protein and induced binding of AP-2 [12].
  • Similarly, cells expressing beta 3 with a substitution at Ser123 also failed to adhere to fibrinogen and did not bind RGD peptide or mAb PAC1 [24].

Physical interactions of Adcyap1r1

  • This possibility is supported by the observation that cytosolic endogenous PACAP in spermatids was co-immunoprecipitated with the cytosolic PAC1-R [21].

Regulatory relationships of Adcyap1r1


Other interactions of Adcyap1r1


Analytical, diagnostic and therapeutic context of Adcyap1r1

  • We have applied a gene targeting approach to create a mouse lacking the PAC1 receptor (PAC1(-/-)) [8].
  • Semi-quantitative in situ-hybridization using exon-specific BDNF-probes revealed significantly reduced expression of the exon-III and exon-V-specific transcripts within the hippocampal CA3 region in PAC1-deficient mice [25].
  • However, in contrast to the phase advance seen in wild-type mice, PAC1(-)/- mice responded with phase delays after photic stimulation [27].
  • The most striking finding, which was subsequently confirmed by Western blotting, was a significant reduction of calmodulin (CaM) in wild-type mice as compared with PAC1-/- mice [28].
  • Wild-type mice and mice lacking the PAC1 receptor (PAC1-/-) were light stimulated at early night, and the SCN was examined for proteins that were differentially expressed using two-dimensional gel electrophoresis and identification by tandem mass spectrometry [28].


  1. Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor. Martinez, C., Abad, C., Delgado, M., Arranz, A., Juarranz, M.G., Rodriguez-Henche, N., Brabet, P., Leceta, J., Gomariz, R.P. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Analysis of the role of the PAC1 receptor in neutrophil recruitment, acute-phase response, and nitric oxide production in septic shock. Martínez, C., Juarranz, Y., Abad, C., Arranz, A., Miguel, B.G., Rosignoli, F., Leceta, J., Gomariz, R.P. J. Leukoc. Biol. (2005) [Pubmed]
  3. Impaired long-term potentiation in vivo in the dentate gyrus of pituitary adenylate cyclase-activating polypeptide (PACAP) or PACAP type 1 receptor-mutant mice. Matsuyama, S., Matsumoto, A., Hashimoto, H., Shintani, N., Baba, A. Neuroreport (2003) [Pubmed]
  4. A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells. Sharma, A., Walters, J., Gozes, Y., Fridkin, M., Brenneman, D., Gozes, I., Moody, T.W. J. Mol. Neurosci. (2001) [Pubmed]
  5. Pulmonary hypertension and right heart failure in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. Otto, C., Hein, L., Brede, M., Jahns, R., Engelhardt, S., Gröne, H.J., Schütz, G. Circulation (2004) [Pubmed]
  6. Altered emotional behavior in PACAP-type-I-receptor-deficient mice. Otto, C., Martin, M., Wolfer, D.P., Lipp, H.P., Maldonado, R., Schütz, G. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  7. Altered social behavior in pituitary adenylate cyclase-activating polypeptide type I receptor-deficient mice. Nicot, A., Otto, T., Brabet, P., Dicicco-Bloom, E.M. J. Neurosci. (2004) [Pubmed]
  8. PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance. Jamen, F., Persson, K., Bertrand, G., Rodriguez-Henche, N., Puech, R., Bockaert, J., Ahrén, B., Brabet, P. J. Clin. Invest. (2000) [Pubmed]
  9. Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: potential role in patterning and neurogenesis. Waschek, J.A., Casillas, R.A., Nguyen, T.B., DiCicco-Bloom, E.M., Carpenter, E.M., Rodriguez, W.I. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways. Dorsam, R.T., Kim, S., Murugappan, S., Rachoor, S., Shankar, H., Jin, J., Kunapuli, S.P. Blood (2005) [Pubmed]
  11. Induction of fibrinogen binding and platelet aggregation as a potential intrinsic property of various glycoprotein IIb/IIIa (alphaIIbbeta3) inhibitors. Peter, K., Schwarz, M., Ylänne, J., Kohler, B., Moser, M., Nordt, T., Salbach, P., Kübler, W., Bode, C. Blood (1998) [Pubmed]
  12. Activation of the mitogen-activated protein kinase pathway induces transcription of the PAC-1 phosphatase gene. Grumont, R.J., Rasko, J.E., Strasser, A., Gerondakis, S. Mol. Cell. Biol. (1996) [Pubmed]
  13. Ectopic alphaIIbbeta3 integrin signaling involves 12-lipoxygenase- and PKC-mediated serine phosphorylation events in melanoma cells. Rásó, E., Tóvári, J., Tóth, K., Paku, S., Trikha, M., Honn, K.V., Tímár, J. Thromb. Haemost. (2001) [Pubmed]
  14. Ligand-mimetic anti-alphaIIb beta3 antibody PAC-1 inhibits tyrosine signaling, proliferation and lung colonization of melanoma cells. Rásó, E., Tóvári, J., Ladányi, A., Varga, N., Tímár, J. Pathol. Oncol. Res. (2005) [Pubmed]
  15. Expression of PACAP, and PACAP type 1 (PAC1) receptor mRNA during development of the mouse embryo. Sheward, W.J., Lutz, E.M., Copp, A.J., Harmar, A.J. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  16. Up-regulation of the PACAP type-1 receptor (PAC1) promoter by neurotrophins in rat PC12 cells and mouse cerebellar granule cells via the Ras/mitogen-activated protein kinase cascade. Jamen, F., Bouschet, T., Laden, J.C., Bockaert, J., Brabet, P. J. Neurochem. (2002) [Pubmed]
  17. Structure of the gene encoding the mouse pituitary adenylate cyclase-activating polypeptide receptor. Aino, H., Hashimoto, H., Ogawa, N., Nishino, A., Yamamoto, K., Nogi, H., Nagata, S., Baba, A. Gene (1995) [Pubmed]
  18. VIP and PACAP induce selective neuronal differentiation of mouse embryonic stem cells. Cazillis, M., Gonzalez, B.J., Billardon, C., Lombet, A., Fraichard, A., Samarut, J., Gressens, P., Vaudry, H., Rostène, W. Eur. J. Neurosci. (2004) [Pubmed]
  19. Embryonic expression of pituitary adenylyl cyclase-activating polypeptide and its selective type I receptor gene in the frog Xenopus laevis neural tube. Hu, Z., Lelievre, V., Rodriguez, W.I., Tam, J., Cheng, J.W., Cohen-Cory, S., Waschek, J.A. J. Comp. Neurol. (2001) [Pubmed]
  20. Pituitary adenylate cyclase-activating polypeptide promotes differentiation of mouse neural stem cells into astrocytes. Ohno, F., Watanabe, J., Sekihara, H., Hirabayashi, T., Arata, S., Kikuyama, S., Shioda, S., Nakaya, K., Nakajo, S. Regul. Pept. (2005) [Pubmed]
  21. Pituitary adenylate cyclase activating polypeptide-mediated intracrine signaling in the testicular germ cells. Li, M., Funahashi, H., Mbikay, M., Shioda, S., Arimura, A. Endocrine (2004) [Pubmed]
  22. Markedly reduced chronic nociceptive response in mice lacking the PAC1 receptor. Jongsma, H., Pettersson, L.M., Zhang Yz, n.u.l.l., Reimer, M.K., Kanje, M., Waldenström, A., Sundler, F., Danielsen, N. Neuroreport (2001) [Pubmed]
  23. Differential expression of glutamate transporters EAAT1 and EAAT2 in mice deficient for PACAP-type I receptor. Zink, M., Schmitt, A., Henn, F.A., Gass, P. Journal of neural transmission (Vienna, Austria : 1996) (2004) [Pubmed]
  24. Mutation of a ligand binding domain of beta 3 integrin. Integral role of oxygenated residues in alpha IIb beta 3 (GPIIb-IIIa) receptor function. Bajt, M.L., Loftus, J.C. J. Biol. Chem. (1994) [Pubmed]
  25. Reduced expression of brain-derived neurotrophic factor in mice deficient for pituitary adenylate cyclase activating polypeptide type-I-receptor. Zink, M., Otto, C., Zörner, B., Zacher, C., Schütz, G., Henn, F.A., Gass, P. Neurosci. Lett. (2004) [Pubmed]
  26. The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice. Persson, K., Ahrén, B. Acta Physiol. Scand. (2002) [Pubmed]
  27. Dissociation between light-induced phase shift of the circadian rhythm and clock gene expression in mice lacking the pituitary adenylate cyclase activating polypeptide type 1 receptor. Hannibal, J., Jamen, F., Nielsen, H.S., Journot, L., Brabet, P., Fahrenkrug, J. J. Neurosci. (2001) [Pubmed]
  28. Altered calmodulin response to light in the suprachiasmatic nucleus of PAC1 receptor knockout mice revealed by proteomic analysis. Fahrenkrug, J., Hannibal, J., Honoré, B., Vorum, H. J. Mol. Neurosci. (2005) [Pubmed]
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