More information on this family may be found on the IUPHAR-DB family and introduction pages.
Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors (nomenclature recommended by the NC-IUPHAR Subcommittee on Vasoactive Intestinal Peptide Receptors, [5]) are activated by the endogenous peptides VIP, PACAP-38, PACAP-27, peptide histidine isoleucineamide (PHI), peptide histidine methionineamide (PHM) and peptide histidine valine (PHV). “PACAP type II receptors” (VPAC1 and VPAC2 receptors) display comparable affinity for PACAP and VIP, whereas PACAP-27 and PACAP-38 are >100 fold more potent than VIP as agonists of most isoforms of the PAC1 receptor. However, one splice variant of the human PAC1 receptor has been reported to respond to PACAP-38, PACAP-27 and VIP with comparable affinity [1]. PG 99-465 [8] has been used as a selective VPAC2 receptor antagonist in a number of physiological studies, but has been reported to have significant activity at VPAC1 and PAC1 receptors [2]. The selective PAC1 receptor agonist maxadilan, was extracted from the salivary glands of sand flies (Lutzomyia longipalpis) and has no sequence homology to VIP or PACAP [9]. Two deletion variants of maxadilan, M65 [13] and Max.d.4 [10] have been reported to be PAC1 receptor antagonists, but these peptides have not been extensively characterised.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Couvineau, A; Ceraudo, E; Tan, YV; Laburthe, M. (2010) VPAC1 receptor binding site: contribution of photoaffinity labeling approach. Neuropeptides, 44 (2): 127-32. [PMID:20031208]
Dickson, L; Finlayson, K. (2009) VPAC and PAC receptors: From ligands to function. Pharmacol. Ther., 121 (3): 294-316. [PMID:19109992]
Gonzalez-Rey, E; Varela, N; Chorny, A; Delgado, M. (2007) Therapeutical approaches of vasoactive intestinal peptide as a pleiotropic immunomodulator. Curr. Pharm. Des., 13 (11): 1113-39. [PMID:17430175]
Groneberg, DA; Rabe, KF; Fischer, A. (2006) Novel concepts of neuropeptide-based drug therapy: vasoactive intestinal polypeptide and its receptors. Eur. J. Pharmacol., 533 (1-3): 182-94. [PMID:16473346]
Harmar, A. J., Arimura, A., Gozes, I., Journot, L., Laburthe, M., Pisegna, J. R., Rawlings, S. R., Robberecht, P., Said, S. I., Sreedharan, S. P., Wank, S. A. and Waschek, J. A. (1998) International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev, 50: 265-270. [PMID:9647867]
Hill, JM. (2007) Vasoactive intestinal peptide in neurodevelopmental disorders: therapeutic potential. Curr. Pharm. Des., 13 (11): 1079-89. [PMID:17430171]
Laburthe, M; Couvineau, A; Tan, V. (2007) Class II G protein-coupled receptors for VIP and PACAP: structure, models of activation and pharmacology. Peptides, 28 (9): 1631-9. [PMID:17574305]
Moody, TW; Ito, T; Osefo, N; Jensen, RT. (2011) VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studies. Curr Opin Endocrinol Diabetes Obes, 18 (1): 61-7. [PMID:21157320]
Nakata, M; Yada, T. (2007) PACAP in the glucose and energy homeostasis: physiological role and therapeutic potential. Curr. Pharm. Des., 13 (11): 1105-12. [PMID:17430174]
Schytz, HW; Olesen, J; Ashina, M. (2010) The PACAP receptor: a novel target for migraine treatment. Neurotherapeutics, 7 (2): 191-6. [PMID:20430318]
Vaudry, D; Falluel-Morel, A; Bourgault, S; Basille, M; Burel, D; Wurtz, O; Fournier, A; Chow, BK; Hashimoto, H; Galas, L; et al.. (2009) Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol. Rev., 61 (3): 283-357. [PMID:19805477]
1. Dautzenberg, F. M., Mevenkamp, G., Wille, S. and Hauger, R. L. (1999) N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants. J Neuroendocrinol, 11: 941-949. [PMID:10583729]
2. Dickson, L; Aramori, I; McCulloch, J; Sharkey, J; Finlayson, K. (2006) A systematic comparison of intracellular cyclic AMP and calcium signalling highlights complexities in human VPAC/PAC receptor pharmacology. Neuropharmacology, 51 (6): 1086-98. [PMID:16930633]
3. Gourlet, P., De Neef, P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (1997) In vitro properties of a high affinity selective antagonist of the VIP1 receptor. Peptides, 18: 1555-1560. [PMID:9437716]
4. Gourlet, P., Vertongen, P., Vandermeers, A., Vandermeers-Piret, M. C., Rathe, J., De Neef, P., Waelbroeck, M. and Robberecht, P. (1997) The long-acting vasoactive intestinal polypeptide agonist RO 25-1553 is highly selective of the VIP2 receptor subclass. Peptides, 18: 403-408. [PMID:9145428]
5. Harmar, A. J., Arimura, A., Gozes, I., Journot, L., Laburthe, M., Pisegna, J. R., Rawlings, S. R., Robberecht, P., Said, S. I., Sreedharan, S. P., Wank, S. A. and Waschek, J. A. (1998) International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev, 50: 265-270. [PMID:9647867]
6. Juarranz, M. G., Van, Rampelbergh J., Gourlet, P., De, Neef P., Cnudde, J., Robberecht, P. and Waelbroeck, M. (1999) Different vasoactive intestinal polypeptide receptor domains are involved in the selective recognition of two VPAC2-selective ligands. Mol Pharmacol, 56: 1280-1287. [PMID:10570056]
7. Moody, T.W., Jensen, R.T., Fridkin, M. and Gozes, I. (2002) (N-stearyl, norleucine17)VIPhybrid is a broad spectrum vasoactive intestinal peptide receptor antagonist. J Mol Neurosci., 18: 29-35. [PMID:11931347]
8. Moreno, D., Gourlet, P., De, Neef P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (2000) Development of selective agonists and antagonists for the human vasoactive intestinal polypeptide VPAC2 receptor. Peptides, 21: 1543-1549. [PMID:11068102]
9. Moro, O. and Lerner, E. A. (1997) Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist. J Biol Chem, 272: 966-970. [PMID:8995389]
10. Moro, O., Wakita, K., Ohnuma, M., Denda, S., Lerner, E. A. and Tajima, M. (1999) Functional characterization of structural alterations in the sequence of the vasodilatory peptide maxadilan yields a pituitary adenylate cyclase-activating peptide type 1 receptor-specific antagonist. J Biol Chem, 274: 23103-23110. [PMID:10438479]
11. Nicole, P., Lins, L., Rouyer-Fessard, C., Drouot, C., Fulcrand, P., Thomas, A., Couvineau, A., Martinez, J., Brasseur, R. and Laburthe, M. (2000) Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide. J Biol Chem., 275: 24003-24012. [PMID:10801840]
12. Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H. and Journot, L. (1993) Differential signal transduction by five splice variants of the PACAP receptor. Nature, 365: 170-175. [PMID:8396727]
13. Uchida, D; Tatsuno, I; Tanaka, T; Hirai, A; Saito, Y; Moro, O; Tajima, M. (1998) Maxadilan is a specific agonist and its deleted peptide (M65) is a specific antagonist for PACAP type 1 receptor. Ann. N. Y. Acad. Sci., 865: 253-8. [PMID:9928019]
14. Van Rampelbergh, J., Gourlet, P., De Neef, P., Robberecht, P. and Waelbroeck, M. (1996) Properties of the pituitary adenylate cyclase-activating polypeptide I and II receptors, vasoactive intestinal peptide1, and chimeric amino-terminal pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide1 receptors: evidence for multiple receptor states. Mol Pharmacol, 50: 1596-1604. [PMID:8967982]
15. Xia, M., Sreedharan, S. P., Bolin, D. R., Gaufo, G. O. and Goetzl, E. J. (1997) Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor. J Pharmacol Exp Ther, 281: 629-633. [PMID:9152366]
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Subtypes of PAC1 receptors have been proposed based on tissue differences in the potencies of PACAP-27 and PACAP-38; these might result from differences in G protein coupling and second messenger mechanisms [14], or from alternative splicing of PAC1 receptor mRNA [12].