Overview: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors (nomenclature recommended by the NC-IUPHAR Subcommittee on Vasoactive Intestinal Peptide Receptors, Harmar et al., 1998) are activated by the endogenous peptides VIP, PACAP1–38, PACAP1–27, peptide histidine isoleucineamide (PHI), peptide histidine methionineamide (PHM), peptide histidine valine and growth hormone-releasing factor (GRF). PACAP Type II receptors have been defined as those for which PACAP and VIP display comparable affinity. Both VPAC1 and VPAC2 meet this definition. [Arg16]chicken secretin is an agonist at both VPAC1 and secretin receptors, but can be used as an agonist at VPAC1 receptors in tissues that do not express secretin receptors (Gourlet et al., 1997a). PACAP6–38 also shows significant affinity for VPAC2 receptors. Helodermin discriminates VPAC1 and VPAC2 in a species-dependent manner (Gourlet et al., 1998).
| Nomenclature | VPAC1 | VPAC2 | PAC1 |
|---|---|---|---|
| Other names | VIP1/PACAP, VIP, VIP1, PACAP Type II, PVR2 | VIP2/PACAP, VIP2, PACAP3, PVR2 | PACAP, PACAP Type I, PVR1 |
| Ensembl ID | ENSG00000114812 | ENSG00000106018 | ENSG00000078549 |
| Principal transduction | Gs | Gs | Gs |
| Rank order of potency | VIP, PACAP-(1–27) = PACAP-(1–38) > GRF >> PHI >> secretin | VIP, PACAP-(1–38) > PACAP-(1–27) > PHI >> GRF, secretin | PACAP-(1–27), PACAP-(1–38) >> VIP > PHI |
| Selective agonists | [Arg16]chicken secretin, [Lys15,Arg16,Leu27]VIP-(1–7)-GRF-(8–27)-NH2 | Ro251553 (Gourlet et al., 1997a,b;), Ro251392 (Xia et al., 1997) | Maxadilan (Moro and Lerner, 1997) |
| Selective antagonists | [Ac-His1,D-Phe2,Lys15,Arg16]VIP-(3–7)-GRF-(8–27)-NH2 (Gourlet et al., 1997a) | – | PACAP-(6–38) |
| Probes | [125I]-VIP, [125I]-PACAP | [125I]-VIP, [125I]-PACAP | [125I]-PACAP |
Subtypes of PAC1 receptors have been proposed based on tissue differences in the potencies of PACAP1–27 and PACAP1–38; these might result from differences in G protein coupling and second messenger mechanisms (Van Ramplebergh et al., 1996), or from alternative splicing of PAC1 receptor mRNA (Spengler et al., 1993).
Glossary
Abbreviations:
- Ro251392
Ac-His1[Glu8,OCH3-Tyr10,Lys12,Nle17,Ala19,Asp25,Leu26,Lys27,28]VIP (cyclo 21–25)
- Ro251553
Ac-His1[Glu8,Lys12,Nle17,Ala19,Asp25,Leu26,Lys27,28,Gly29,30,Thr31]VIP-NH2 (cyclo 21–25)
Further Reading
Abad C, Gomariz RP, Waschek JA (2006). Neuropeptide mimetics and antagonists in the treatment of inflammatory disease: focus on VIP and PACAP. Curr Top Med Chem6: 151–163.
Gonzalez-Rey E, Varela N, Chorny A, Delgado M (2007). Therapeutical approaches of vasoactive intestinal peptide as a pleiotropic immunomodulator. Curr Pharm Des13: 1113–1139.
Groneberg DA, Rabe KF, Fischer A (2006). Novel concepts of neuropeptide-based drug therapy: vasoactive intestinal polypeptide and its receptors. Eur J Pharmacol533: 182–194.
Harmar AJ, Arimura A, Gozes I, Journot L, Laburthe M, Pisegna JR et al. (1998). International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev50: 265–270.
Hill JM (2007). Vasoactive intestinal peptide in neurodevelopmental disorders: therapeutic potential. Curr Pharm Des13: 1079–1089.
Laburthe M, Couvineau A, Tan V (2007). Class II G protein-coupled receptors for VIP and PACAP: structure, models of activation and pharmacology. Peptides28: 1631–1639.
Nakata M, Yada T (2007). PACAP in the glucose and energy homeostasis: physiological role and therapeutic potential. Curr Pharm Des13: 1105–1112.
References
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