ADCYAP1R1 explained

Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC₁, is a protein that in humans is encoded by the ADCYAP1R1 gene. This receptor binds pituitary adenylate cyclase activating peptide.^{[1] [2]}

Function

PAC₁ is a membrane-associated protein and shares significant homology with members of the G-protein coupled class B glucagon/secretin receptor family.^[3] This receptor mediates diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. Alternative splicing of two exons of this gene generates four major splice variants, but their full-length nature has not been determined.^[4] PAC₁ is expressed in the adrenal medulla, pancreatic acini, uterus, myenteric plexus and brain.^{[5] [6] [7]} It is also expressed in the trigeminal, otic and superior cervical ganglia (prejunctional) and cerebral arteries (postjunctional).^[8]

Further reading

• Stoffel M, Espinosa R, Trabb JB, Le Beau MM, Bell GI . Human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R): localization to chromosome band 7p14 and integration into the cytogenetic, physical, and genetic map of chromosome 7 . Genomics . 23 . 3 . 697–9 . Oct 1994 . 7851900 . 10.1006/geno.1994.1560 .
• Ogi K, Miyamoto Y, Masuda Y, Habata Y, Hosoya M, Ohtaki T, Masuo Y, Onda H, Fujino M . Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor . Biochemical and Biophysical Research Communications . 196 . 3 . 1511–21 . Nov 1993 . 7902709 . 10.1006/bbrc.1993.2423 .
• Ohtaki T, Masuda Y, Ishibashi Y, Kitada C, Arimura A, Fujino M . Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide . The Journal of Biological Chemistry . 268 . 35 . 26650–7 . Dec 1993 . 10.1016/S0021-9258(19)74361-0 . 8253796 . free .
• Pisegna JR, Wank SA . Cloning and characterization of the signal transduction of four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor. Evidence for dual coupling to adenylate cyclase and phospholipase C . The Journal of Biological Chemistry . 271 . 29 . 17267–74 . Jul 1996 . 8663363 . 6721843 . 10.1074/jbc.271.29.17267 . free .
• Pantaloni C, Brabet P, Bilanges B, Dumuis A, Houssami S, Spengler D, Bockaert J, Journot L . Alternative splicing in the N-terminal extracellular domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor modulates receptor selectivity and relative potencies of PACAP-27 and PACAP-38 in phospholipase C activation . The Journal of Biological Chemistry . 271 . 36 . 22146–51 . Sep 1996 . 8703026 . 10.1074/jbc.271.36.22146 . free .
• Solano RM, Carmena MJ, Carrero I, Cavallaro S, Roman F, Hueso C, Travali S, Lopez-Fraile N, Guijarro LG, Prieto JC . Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate . Endocrinology . 137 . 7 . 2815–22 . Jul 1996 . 8770902 . 10.1210/en.137.7.2815 . free .
• Wei Y, Mojsov S . Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology . Journal of Neuroendocrinology . 8 . 11 . 811–7 . Nov 1996 . 8933357 . 10.1046/j.1365-2826.1996.05191.x . 22302790 .
• Brabet P, Diriong S, Journot L, Bockaert J, Taviaux S . Localization of the human pituitary adenylate cyclase-activating polypeptide receptor (PACAP1-R) gene to 7p15-p14 by fluorescence in situ hybridization . Genomics . 38 . 1 . 100–2 . Nov 1996 . 8954788 . 10.1006/geno.1996.0600 .
• Yon L, Breault L, Contesse V, Bellancourt G, Delarue C, Fournier A, Lehoux JG, Vaudry H, Gallo-Payet N . Localization, characterization, and second messenger coupling of pituitary adenylate cyclase-activating polypeptide receptors in the fetal human adrenal gland during the second trimester of gestation . The Journal of Clinical Endocrinology and Metabolism . 83 . 4 . 1299–305 . Apr 1998 . 10.1210/jcem.83.4.4690 . 9543159 .
• Steinhoff M, McGregor GP, Radleff-Schlimme A, Steinhoff A, Jarry H, Schmidt WE . Identification of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type 1 receptor in human skin: expression of PACAP-38 is increased in patients with psoriasis . Regulatory Peptides . 80 . 1–2 . 49–55 . Mar 1999 . 10235634 . 10.1016/S0167-0115(99)00010-5 . 8591698 .
• Zeng N, Athmann C, Kang T, Lyu RM, Walsh JH, Ohning GV, Sachs G, Pisegna JR . PACAP type I receptor activation regulates ECL cells and gastric acid secretion . The Journal of Clinical Investigation . 104 . 10 . 1383–91 . Nov 1999 . 10562300 . 409843 . 10.1172/JCI7537 .
• Dautzenberg FM, Mevenkamp G, Wille S, Hauger RL . N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants . Journal of Neuroendocrinology . 11 . 12 . 941–9 . Dec 1999 . 10583729 . 10.1046/j.1365-2826.1999.00411.x . 35761617 .
• Scaldaferri ML, Modesti A, Palumbo C, Ulisse S, Fabbri A, Piccione E, Frajese G, Moretti C . Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta . Endocrinology . 141 . 3 . 1158–67 . Mar 2000 . 10698193 . 10.1210/endo.141.3.7346 . free .
• Busto R, Prieto JC, Bodega G, Zapatero J, Carrero I . Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung . Peptides . 21 . 2 . 265–9 . Feb 2000 . 10764955 . 10.1016/S0196-9781(99)00202-8 . 44951090 .
• Knutsson M, Edvinsson L . Distribution of mRNA for VIP and PACAP receptors in human cerebral arteries and cranial ganglia . NeuroReport . 13 . 4 . 507–9 . Mar 2002 . 11930171 . 10.1097/00001756-200203250-00030 . 30329669 .
• Miampamba M, Germano PM, Arli S, Wong HH, Scott D, Taché Y, Pisegna JR . Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons . Regulatory Peptides . 105 . 3 . 145–54 . May 2002 . 11959368 . 10.1016/S0167-0115(02)00003-4 . 6736535 .
• Le SV, Yamaguchi DJ, McArdle CA, Tachiki K, Pisegna JR, Germano P . PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells . Regulatory Peptides . 109 . 1–3 . 115–25 . Nov 2002 . 12409223 . 10.1016/S0167-0115(02)00194-5 . 6736540 .
• Ronaldson E, Robertson DN, Johnson MS, Holland PJ, Mitchell R, Lutz EM . Specific interaction between the hop1 intracellular loop 3 domain of the human PAC(1) receptor and ARF . Regulatory Peptides . 109 . 1–3 . 193–8 . Nov 2002 . 12409233 . 10.1016/S0167-0115(02)00204-5 . 25745650 .
• Isobe K, Tatsuno I, Yashiro T, Nanmoku T, Takekoshi K, Kawakami Y, Nakai T . Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis . Regulatory Peptides . 110 . 3 . 213–7 . Feb 2003 . 12573802 . 10.1016/S0167-0115(02)00209-4 . 21201447 .

External links

• Web site: VIP and PACAP Receptors: PAC₁ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology .

Notes and References

1. Ogi K, Miyamoto Y, Masuda Y, Habata Y, Hosoya M, Ohtaki T, Masuo Y, Onda H, Fujino M . Molecular cloning and functional expression of a cDNA encoding a human pituitary adenylate cyclase activating polypeptide receptor . Biochemical and Biophysical Research Communications . 196 . 3 . 1511–21 . Nov 1993 . 7902709 . 10.1006/bbrc.1993.2423 .
2. Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H . Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions . Pharmacological Reviews . 52 . 2 . 269–324 . Jun 2000 . 10835102 .
3. Wang J, Song X, Zhang D, Chen X, Li X, Sun Y, Li C, Song Y, Ding Y, Ren R, Harrington EH, Hu LA, Zhong W, Xu C, Huang X, Wang HW, Ma Y . Cryo-EM structures of PAC1 receptor reveal ligand binding mechanism . Cell Res. . 30. 5. 436–445. 2020 . 32047270 . 10.1038/s41422-020-0280-2 . 7196072 . free .
4. Web site: Entrez Gene: ADCYAP1R1 adenylate cyclase activating polypeptide 1 (pituitary) receptor type I.
5. Reubi JC . In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications . Annals of the New York Academy of Sciences . 921 . 1–25 . 2000 . 1 . 11193811 . 10.1111/j.1749-6632.2000.tb06946.x . 2000NYASA.921....1R . 21204750 .
6. Reubi JC, Läderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA . Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin . Cancer Research . 60 . 11 . 3105–12 . Jun 2000 . 10850463 .
7. Yon L, Breault L, Contesse V, Bellancourt G, Delarue C, Fournier A, Lehoux JG, Vaudry H, Gallo-Payet N . Localization, characterization, and second messenger coupling of pituitary adenylate cyclase-activating polypeptide receptors in the fetal human adrenal gland during the second trimester of gestation . The Journal of Clinical Endocrinology and Metabolism . 83 . 4 . 1299–305 . Apr 1998 . 10.1210/jcem.83.4.4690 . 9543159 .
8. Knutsson M, Edvinsson L . Distribution of mRNA for VIP and PACAP receptors in human cerebral arteries and cranial ganglia . NeuroReport . 13 . 4 . 507–9 . Mar 2002 . 11930171 . 10.1097/00001756-200203250-00030 . 30329669 .