VIP and PACAP receptors

Overview

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors are activated by the endogenous peptides VIP, PACAP-38, PACAP-27, peptide histidine isoleucineamide (PHI), peptide histidine methionineamide (PHM) and... [read more] peptide histidine valine (PHV). VPAC₁ and VPAC₂ receptors display comparable affinity for the PACAP peptides, PACAP-27 and PACAP-38, 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 [2] 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 [3]. 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 the PACAP peptides [4]. Two deletion variants of maxadilan, M65 [5] and Max.d.4 [6] have been reported to be PAC₁ receptor antagonists, but these peptides have not been extensively characterised.

References

1. Dautzenberg FM, Mevenkamp G, Wille S, et al. N-terminal splice variants of the type I PACAP receptor: isolation, characterization and ligand binding/selectivity determinants. J Neuroendocrinol 1999;11:941-9.
2. Moreno D, Gourlet P, De Neef P, et al. Development of selective agonists and antagonists for the human vasoactive intestinal polypeptide VPAC(2) receptor. Peptides 2000;21:1543-9.
3. Dickson L, Aramori I, McCulloch J, et al. A systematic comparison of intracellular cyclic AMP and calcium signalling highlights complexities in human VPAC/PAC receptor pharmacology. Neuropharmacology 2006;51:1086-98.
4. Moro O, Lerner EA. Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist. J Biol Chem 1997;272:966-70.
5. Uchida D, Tatsuno I, Tanaka T, et al. Maxadilan is a specific agonist and its deleted peptide (M65) is a specific antagonist for PACAP type 1 receptor. Ann N Y Acad Sci 1998;865:253-8.
6. Moro O, Wakita K, Ohnuma M, et al. 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 1999;274:23103-10.

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