PACAP

J (339), a 28-amino acid peptide, is a member of a family of stmctuially related peptides that includes secretin [1393-25-5] (340), growth hormone releasing factor (GRF), and pituitary adenylate cyclase-activating peptide (PACAP) [137061(341) (83). 

The effects of VIP and PACAP are mediated by three GPCR subtypes, VIP, VIP2, and PACAP receptor, coupled to the activation of adenjiate cyclase (54). The VIP subtype is localized ia the lung, Hver, and iatestiae, and the cortex, hippocampus, and olfactory bulb ia the CNS. The VIP2 receptor is most abundant ia the CNS, ia particular ia the thalamus, hippocampus, hypothalamus, and suprachiasmatic nucleus. PACAP receptors have a wide distribution ia the CNS with highest levels ia the olfactory bulb, the dentate gyms, and the cerebellum (84). The receptor is also present ia the pituitary. The VIP and PACAP receptors have been cloned. 

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. 

PAC-1 (PACAP receptor) VPAC-2 (VIP and PACAP) VPAC-1 VIP and PACAP) GHRH... 

V2 VIP/PACAP (VPAC1 3) prostanoid DP, IP CRFU calcitonin/amylin/CGRP Gj/G0 a2-Adrenoceptor M2/4 muscarinic acetylcholine dopamine D2 4 5HT2 opioid 5, p, K, OFQ ... 

PACAP pituitary adenylyl cyclase-activating peptide PTB phosphotyrosine binding domain... 

Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in the retina exclusively within the RGCs of the retinohypothalamic tract (RHT), and melanopsin was found to co-localize with PACAP in the retina (Hannibal et al... 

The question about whether or not there are additional projections from the retina to the SCN that are melanopsin-negative is a key one. It looks like PACAP and melanopsin together account for most of the RHT. 

Van Gelder The VPAC2 receptor is also the PACAP receptor, and PACAP is the major peptide of RHT. 

Hastings That is right. The confounding possibility is that the receptor has knocked out some RHT sensitivity. But given that we know that in vitro you can put NMD A on a rat slice and get competent phase shifts in the absence of PACAP insensitivity to PACAP is unlikely to be the full reason for impaired circadian entrainment. 

Van Gelder Chris Colwell has data on the PACAP knockout suggesting that they had markedly reduced photosensitivity for phase shifting and entrainment. Although glutamate is sufficient for phase shifting in vitro it may be that in vivo to get normal entrainment or phase response PACAP release is also needed. 

In Hugh Piggin s electrophysiology experiments, did they try resetting manipulations in the dish that avoided PACAP receptors Can the tissue be provoked into something rhythmic This would get around the possibility. One outside possibility is that this is a SCN that had never seen light and had never been synchronized it had never become competent to be rhythmic. 

Capsules 50 mg bufalbifal, 40 mg caffeine, and 325 mg acefaminophen (Amaphen, Anolor-300, Anoquan, Bufacef, Dolmar, Endolor, Esgic, Ezol, Femcef, Medigesic, Pacaps, Repan, Tencef, Triad, Two-Dyne). 

Abad C, Gomariz RP, Waschek JA Neuropeptide mimetics and antagonists in the treatment of inflammatory disease Focus on VIP and PACAP. Curr Top Med Chem 2006 6 151. [PMID 16454764]... 

Finally, peptides such as galanin, leptin, neuropeptide Y, vasoactive intestinal polypeptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) have been identified in various areas of the CNS. These and other peptides may affect various CNS functions, either by acting directly as neurotransmitters or by acting as cotransmitters moderating the effects of other neurotransmitters.7 24,27,34... 

Pozo D. VIP- and PACAP-mediated imtnunomodula-tion as prospective therapeutic tools. Trends Mol Med. 2003 9 211-217. 

Bredow S, Kacsoh B, Obal F Jr, Fang J, Krueger JM. Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP. Brain Res 1994 660 301-308. 

Initial support for Kenakin s hypothesis stemmed from reports of agonist effects that could not be explained with traditional receptor theory. Spengler et al. (11) found that PACAPj 27 had a slightly greater potency than PACAP] 38... 

Spengler D, Waeber C, Pantaloni C, Holsboer F, Bockaert J, Seebuig PH, Joumot L. Differential signal transduction by five splice variants of the PACAP receptor. Nature 1999 365 170-175. 

Agarwal, A., Halvorson, L.M., and Legradi, G. (2005) Pituitary adenylate cyclase-activating polypeptide (PACAP) mimics neuroendocrine and behavioral manifestations of stress Evidence for PKA-mediated expression of the corticotropin-releasing hormone (CRH) gene. Brain Res Mol Brain Res. 29 138 45-57. 

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