Vasoactive intestinal protein

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Brenneman DE, Westbrook GL, Fitzgerald SP, Ennist DL, Elkins KL, Ruff MR, Pert CB (1988) Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature 335(6191) 639-642... 

This was the original hypothesis put forward by Lee (1970) and expanded by Ogilvie et al. (1973). Secretory products of N. brasiliensis do indeed decrease the amplitude of contractions of segments of uninfected rat intestine maintained in an organ bath, but a role for AChE in this phenomenon was discounted due to the heat stability of the parasite factor, and the inability to duplicate the effect with AChE from the electric eel (Foster et al., 1994). Subsequent investigations demonstrated that the suppression of contraction could be duplicated by a 30-50 kDa fraction of secreted products, which contained a protein of 30 kDa that was immunologically cross-reactive with mammalian vasoactive intestinal peptide (VIP). Moreover, an antibody to porcine VIP significantly reduced the inhibitory effect of parasite-secreted products on contraction in vitro (Foster and Lee, 1996). 

Foster, N. and Lee, D.L. (1996) A vasoactive intestinal polypeptide-like protein excreted/secreted by Nippostrongylus brasiliensis and its effect on contraction of uninfected rat intestine. Parasitology 112, 97-104. 

Grinninger, C., Wang, W., Bastani Oskoui, K., Voice, J.K., and Goetzl, E.J. 2004. A natural variant type ii g protein-coupled receptor for vasoactive intestinal peptide with altered function. J Biol Chem 279(39) 40259 10262. 

Before the era of synuclein immunocytochemistry, Qualman et al. (1984) observed in a postmortem study LBs in the esophageal Auerbach plexus of two dysphagic PD patients but not in Meissner s plexus. Subsequently, Wakabayashi et al. (1988) reported LBs and LNs in both plexuses of clinically diagnosed PD patients and asymptomatic incidental cases. In the gut, the bulk of the proteins were observed in cellular processes and cell bodies of vasoactive intestinal polypeptide (VIPergic) neurons (Wakabayashi et al., 1988,1993). 

Coy DH, Gardner J. Solid-phase synthesis of porcine vasoactive intestinal peptide. Int. J. Peptide Protein Res. 1980 15 73-78. Brazean P, Vale W, Bnrgns R, Ling N, Bntcher M, Rivier J, Gnillemin R. Hypothalamic polypeptide that inhibits the secretion of immnnoreactive pitnitary growth hormone. Science 1973 179 77-79. 

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