Discovery of PACAP and Its Receptors in the Brain

Overview

Journal J Headache Pain

Publisher Biomed Central

Date 2018 Apr 6

PMID 29619773

Citations 63

Authors

Takahiro Hirabayashi

Tomoya Nakamachi

Seiji Shioda

Affiliations

Soon will be listed here.

Abstract

Pituitary adenylate-cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. PACAP shows particularly high homology (~ 68%) to VIP. Because of the high homology of the amino acid sequences of PACAP and VIP, these peptides share three class B-G-protein coupled receptors: the PAC1-Receptor (PAC1-R), the VPAC1-Receptor (VPAC1-R) and VPAC2-Receptor (VPAC2-R). These receptors have high homology to each other, and their high homology is utilized for these discoveries. This review provides mainly an overview of the history of the discovery of PACAP and its three receptors.

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References

Murase T, Kondo K, Otake K, Oiso Y . Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats. Neuroendocrinology. 1993; 57(6):1092-6. DOI: 10.1159/000126475. View

Hashimoto H, Nogi H, Mori K, Ohishi H, Shigemoto R, Yamamoto K . Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol. 1996; 371(4):567-77. DOI: 10.1002/(SICI)1096-9861(19960805)371:4<567::AID-CNE6>3.0.CO;2-2. View

Li S, Grinevich V, Fournier A, Pelletier G . Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain. Brain Res Mol Brain Res. 1996; 41(1-2):157-62. DOI: 10.1016/0169-328x(96)00086-1. View

Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S . Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron. 1992; 8(4):811-9. DOI: 10.1016/0896-6273(92)90101-i. View

Usdin T, Bonner T, Mezey E . Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology. 1994; 135(6):2662-80. DOI: 10.1210/endo.135.6.7988457. View

Shioda S, Takenoya F, Wada N, Hirabayashi T, Seki T, Nakamachi T . Pleiotropic and retinoprotective functions of PACAP. Anat Sci Int. 2016; 91(4):313-24. DOI: 10.1007/s12565-016-0351-0. View

Cazillis M, Gonzalez B, Billardon C, Lombet A, Fraichard A, Samarut J . VIP and PACAP induce selective neuronal differentiation of mouse embryonic stem cells. Eur J Neurosci. 2004; 19(4):798-808. DOI: 10.1111/j.0953-816x.2004.03138.x. View

Rawlings S, Piuz I, Schlegel W, Bockaert J, Journot L . Differential expression of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide receptor subtypes in clonal pituitary somatotrophs and gonadotrophs. Endocrinology. 1995; 136(5):2088-98. DOI: 10.1210/endo.136.5.7720658. View

Gottschall P, Tatsuno I, Miyata A, Arimura A . Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide. Endocrinology. 1990; 127(1):272-7. DOI: 10.1210/endo-127-1-272. View

10.

Adamou J, Aiyar N, Van Horn S, Elshourbagy N . Cloning and functional characterization of the human vasoactive intestinal peptide (VIP)-2 receptor. Biochem Biophys Res Commun. 1995; 209(2):385-92. DOI: 10.1006/bbrc.1995.1515. View

11.

Freson K, Hashimoto H, Thys C, Wittevrongel C, Danloy S, Morita Y . The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J Clin Invest. 2004; 113(6):905-12. PMC: 362113. DOI: 10.1172/JCI19252. View

12.

Arimura A, Somogyvari-Vigh A, Miyata A, Mizuno K, Coy D, Kitada C . Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology. 1991; 129(5):2787-9. DOI: 10.1210/endo-129-5-2787. View

13.

Lam H, Takahashi K, Ghatei M, Kanse S, Polak J, Bloom S . Binding sites of a novel neuropeptide pituitary-adenylate-cyclase-activating polypeptide in the rat brain and lung. Eur J Biochem. 1990; 193(3):725-9. DOI: 10.1111/j.1432-1033.1990.tb19392.x. View

14.

Morrow J, Lutz E, West K, Fink G, Harmar A . Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). FEBS Lett. 1993; 329(1-2):99-105. DOI: 10.1016/0014-5793(93)80202-6. View

15.

Anderson S, Sawangjaroen K, Curlewis J . Pituitary adenylate cyclase-activating polypeptide acts within the medial basal hypothalamus to inhibit prolactin and luteinizing hormone secretion. Endocrinology. 1996; 137(8):3424-9. DOI: 10.1210/endo.137.8.8754770. View

16.

Pisegna J, Wank S . Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. Proc Natl Acad Sci U S A. 1993; 90(13):6345-9. PMC: 46925. DOI: 10.1073/pnas.90.13.6345. View

17.

Arimura A . Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn J Physiol. 1998; 48(5):301-31. DOI: 10.2170/jjphysiol.48.301. View

18.

Masuo Y, Ohtaki T, Masuda Y, Tsuda M, Fujino M . Binding sites for pituitary adenylate cyclase activating polypeptide (PACAP): comparison with vasoactive intestinal polypeptide (VIP) binding site localization in rat brain sections. Brain Res. 1992; 575(1):113-23. DOI: 10.1016/0006-8993(92)90430-h. View

19.

Vale W, Spiess J, Rivier C, Rivier J . Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981; 213(4514):1394-7. DOI: 10.1126/science.6267699. View

20.

Cavallaro S, Copani A, DAgata V, Musco S, Petralia S, Ventra C . Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons. Mol Pharmacol. 1996; 50(1):60-6. View