PACAP Functions as a Neurotrophic Factora

Arimura, Akira; Somogyvari, A.; Weill, Cheryl L.; Fiore, R.; Tatsuno, Ichiro; Bay, V.; Brenneman, Douglas E.

doi:10.1111/j.1749-6632.1994.tb19825.x

Cited by 175 publications

(102 citation statements)

References 43 publications

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“…Two transduction pathways have been reported for VIP and PACAP: (a) VIP and PACAP can stimulate the production of cAMP (28,29); and (b) recent studies have shown that subnanomolar concentrations of VIP and PACAP stimulate the accumulation of intracellular calcium and increase inositol phosphates in astrocyte cultures (46, 47), and that VIP produces translocation of protein kinase C-␣, -␦ and -isozymes (48).…”

Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Gressèns¹,

Marret²,

Hill³

et al. 1997

J. Clin. Invest.

173

122

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Section: Discussionmentioning

confidence: 99%

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Gressèns¹,

Marret²,

Hill³

et al. 1997

J. Clin. Invest.

173

122

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“…PACAP is a member of the secretin/ glucagon/vasoactive intestinal polypeptide (VIP) family and has the highest sequence similarity to VIP. However, PACAP is 1000 to 10,000 times more potent than VIP in pituitary cells, neurons, and astrocyte cultures (Arimura et al, 1994). PACAP exists in two amidated forms with 38 and 27 amino acid residues, designated PACAP38 and PACAP27, respectively (Miyata et al, 1989(Miyata et al, , 1990.…”

mentioning

confidence: 99%

“…Pituitary adenylate cyclase-activating polypeptide (PACAP) is widely distributed in the peripheral and central nervous system, where PACAP release is reported to serve as a neuronal survival factor (Arimura et al, 1994;Arimura, 1998). PACAP is a member of the secretin/ glucagon/vasoactive intestinal polypeptide (VIP) family and has the highest sequence similarity to VIP.…”

mentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) 38 and PACAP4–6 Are Neuroprotective through Inhibition of NADPH Oxidase: Potent Regulators of Microglia-Mediated Oxidative Stress

Yang

et al. 2006

J Pharmacol Exp Ther

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Microglial activation is implicated in the progressive nature of numerous neurodegenerative diseases, including Parkinson's disease. Using primary rat mesencephalic neuron-glia cultures, we found that pituitary adenylate cyclase-activating polypeptide (PACAP) 38, PACAP27, and its internal peptide, Gly-IlePhe (GIF; PACAP4 -6), are neuroprotective at 10 Ϫ13 M against lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity, as determined by [ 3 H]DA uptake and the number of tyrosine hydroxylase-immunoreactive neurons. PACAP38 and GIF also protected against 1-methyl-4-phenylpyridinium ϩ -induced neurotoxicity but only in cultures containing microglia. PACAP38 and GIF ameliorated the production of microgliaderived reactive oxygen species (ROS), where both LPS-and phorbol 12-myristate 13-acetate-induced superoxide and intracellular ROS were inhibited. The critical role of NADPH oxidase for GIF and PACAP38 neuroprotection against LPS-induced DA neurotoxicity was demonstrated using neuron-glia cultures from mice deficient in NADPH oxidase (PHOX Ϫ/Ϫ ), where PACAP38 and GIF reduced tumor necrosis factor ␣ production and were neuroprotective only in PHOX ϩ/ϩ cultures and not in PHOX Ϫ/Ϫ cultures. Pretreatment with PACAP6 -38 (3 M; PACAP-specific receptor antagonist) was unable to attenuate PACAP38, PACAP27, or GIF (10 Ϫ13 M) neuroprotection. PACAP38 and GIF (10 Ϫ13 M) failed to induce cAMP in neuronglia cultures, supporting that the neuroprotective effect was independent of traditional high-affinity PACAP receptors. Pharmacophore analysis revealed that GIF shares common chemical properties (hydrogen bond acceptor, positive ionizable, and hydrophobic regions) with other subpicomolar-acting compounds known to inhibit NADPH oxidase: naloxone, dextromethorphan, and Gly-Gly-Phe. These results indicate a common high-affinity site of action across numerous diverse peptides and compounds, revealing a basic neuropeptide regulatory mechanism that inhibits microglia-derived oxidative stress and promotes neuron survival.Parkinson's disease (PD) is characterized by the progressive and selective degeneration of dopaminergic (DA) neurons in the substantia nigra, but the etiology and the precise mechanisms underlying the selective destruction of the nigrostriatal dopaminergic pathway are unknown. Recently, increasing evidence from clinical (McGeer et al., 1988) and animal studies (Castano et al., 1998;Sriram et al., 2002) suggests the involvement of inflammation in the pathogenesis of PD. Inflammation in the brain is characterized by the activation of microglia (Aloisi, 1999), the resident innate immune cells in the central nervous system. Microglia are activated by a diverse list of environmental (particulate matter, pesticides, heavy metals) and endogenous triggers (␣-synuclein, ␤-amyloid) to produce reactive oxygen species (ROS) and/or proinflammatory factors, which are toxic to

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“…PACAP is widely distributed in mammalians with the highest concentration in the central nervous system (Koves et al, 1990;Arimura et al, 1991). It is a hypophysiotropic hormone and also functions as neurotransmitter, neuromodulator, and neurotrophic factor in the central nervous system (for details see the following reviews : Arimura et al, 1994;Arimura and Shioda, 1995). More than one subtype of PACAP receptors have been described so far.…”

mentioning

confidence: 99%

Photoaffinity Labeling Analysis of the Interaction of Pituitary Adenylate‐Cyclase‐Activating Polypeptide (PACAP) with the PACAP Type I Receptor

Cao

Kojro

Gimpl

et al. 1997

European Journal of Biochemistry

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To identify residues and domains of the peptide hormone pituitary adenylate-cyclase-activating polypeptide (PACAP) that interact with the type I receptor, two photoreactive analogues of PACAP-( 1-27)-peptide were synthesized using solid-phase peptide synthesis. Phe6 or Tyr22 within the PACAP sequence were replaced by p-benzoyl-L-phenylalanine (Bz-Phe) thus creating two PACAP derivatives with a photoreactive amino acid in either the disordered N-terminal or the helical C-terminal part of the peptide. The ligand-binding properties and the efficiencies of these peptide analogues as photolabels were tested for pig brain PACAP receptors.

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PACAP Functions as a Neurotrophic Factora

Cited by 175 publications

References 43 publications

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) 38 and PACAP4–6 Are Neuroprotective through Inhibition of NADPH Oxidase: Potent Regulators of Microglia-Mediated Oxidative Stress

Photoaffinity Labeling Analysis of the Interaction of Pituitary Adenylate‐Cyclase‐Activating Polypeptide (PACAP) with the PACAP Type I Receptor

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