Pituitary adenylate cyclase-activating polypeptide protects rat-cultured cortical neurons from glutamate-induced cytotoxicity

Morio, Hiroshi; Tatsuno, Ichiro; Hirai, Aizan; Tamura, Yasushi; Saitō, Yasushi

doi:10.1016/s0006-8993(96)00920-1

Cited by 107 publications

(67 citation statements)

References 40 publications

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“…Several lines of evidence suggest that PACAP acts as a neurotrophic factor (12)(13)(14) and plays a role in mammalian neurogenesis (40). For instance, the PAC 1 receptor is expressed at very high levels in ventricular zones throughout the embryonic neuraxis, and PACAP likely regulates the development of the general features of the neuronal phenotype (40).…”

Section: Discussionmentioning

confidence: 99%

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Hashimoto

Shintani²,

Tanaka³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

364

298

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Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved remarkably during evolution and is widely expressed in the mammalian brain. In Drosophila, mutation of the PACAP homologue results in behavioral defects, including impaired olfaction-associated learning and changes in ethanol sensitivity. Here, we report the generation of mice lacking the PACAP gene (PACAP ؊/؊ ). PACAP ؊/؊ mice were born in the expected Mendelian ratios but had a high early-mortality rate. The surviving adult PACAP ؊/؊ mice displayed remarkable behavioral changes; they exhibited hyperactive and explosive jumping behaviors in an open field, increased exploratory behavior, and less anxiety in the elevated plus maze, emergence, and novel-object tests. Analysis of PACAP ؊/؊ mice brains revealed that the serotonin metabolite 5-hydroxyindoleacetic acid was slightly decreased in the cortex and striatum compared with wild-type mice. The present study provides evidence that PACAP plays a previously uncharacterized role in the regulation of psychomotor behaviors. P ituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP)͞ secretin͞glucagon family of peptides and exists in two amidated forms, PACAP38 and PACAP27, that share an identical 27-aa N terminus and are alternatively processed from a 176-aa precursor called preproPACAP (1, 2). The primary structure of PACAP38 has been conserved significantly during evolution from protochordates to mammals, suggesting that the peptide exerts important activities throughout the vertebrate phylum (1, 2). In Drosophila, recent molecular cloning and transgenic rescue experiments in the memory-mutant amnesiac, which has behavioral defects that include impaired olfaction-associated learning and changes in ethanol sensitivity, demonstrated that the amnesiac gene encodes a neuropeptide homologous to vertebrate PACAP (3, 4). In addition, mammalian PACAP activated both the cAMP and Ras͞Raf signal-transduction pathways in Drosophila neurons, suggesting a neuromodulatory role of amnesiac (Drosophila PACAP) in specific neuronal populations (5). In mammals, PACAP occurs in neuronal elements, where it acts as a pleiotropic neuropeptide via three heptahelical G protein-linked receptors-one PACAP-specific (PAC 1 ) receptor and two receptors that it shares with VIP (VPAC 1 and VPAC 2 ). PACAP stimulates several different signaling cascades in neurons, leading to the activation of adenylate cyclase, phospholipase C, and mitogen-activated protein kinase and the mobilization of calcium (1, 2, 6). Histochemical studies have shown that PACAP immunoreactivity is observed in several brain regions, including the dopamine (DA) and serotonin (5-HT) systems, with high concentrations found in the nucleus accumbens, hypothalamus, amygdala, substantia nigra, and dorsal raphe (7-9). PAC 1 receptor also is expressed throughout the target areas of both the mesocorticolimbic and nigrostriatal DA systems as well as 5-HT system (10). In addition, VPAC 1 and VPAC 2 recepto...

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Section: Discussionmentioning

confidence: 99%

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Hashimoto

Shintani²,

Tanaka³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

364

298

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“…This is in accordance with previous findings in hot plate and formalin tests conducted by Spampinato et al [206] and recent results that of Elhabazi et al [50]. In our experiments no linear dose-response curve, but rather an inverted bell-shaped response was observed, which is well known in the literature, and has already been described in case of endomorphins [22] and other neuropeptides [146]. Possible mechanism for this phenomenon could be homologous desensitization by G-protein coupled receptor kinases that phosphorylate already activated receptors thus lowering the responsiveness of the cell specifically to ligands of those receptors [54,173].…”

Section: Discussionsupporting

confidence: 94%

“…Increasing doses of KP-13 exhibited a bell-shaped dose-response curve. This type of response is well-known in the literature and has been described in case of other neuropeptides [146,22]. Since KISS1R has been found abundantly in locomotor centres of key importance such as the striatum and Amy [148,98,106], therefore it is plausible that KP-13 stimulated these regions directly.…”

Section: Discussionmentioning

confidence: 58%

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

Csabafi¹

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“…PACAPalso stimulates calcium mobilization (Gonzalez et al, 1996;Mei, 1999) and blocks transient potassium currents (Zerr and Feltz, 1994), two processes closely involved in the regulation of programmed cell death. PACAP can also directly protect cultured cortical neurons from the cytotoxic effects of high concentrations of glutamate (Morio et al, 1996). A neuroprotective effect of PACAP on glutamate-induced neurotoxicity also has been reported in cultured retinal neurons (Shoge et al, 1999).…”

Section: Pituitary Adenylate Cyclase Activating Peptide (Pacap)mentioning

confidence: 90%

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

Martin

Maturana²,

Brenneman

et al. 2005

NMM

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G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class II GPCRs which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class II GPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class II GPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class II GPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders.

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Pituitary adenylate cyclase-activating polypeptide protects rat-cultured cortical neurons from glutamate-induced cytotoxicity

Cited by 107 publications

References 40 publications

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)

Kisspeptin modulates the activity of the stress system and associated behaviours, the body temperature and nociception

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

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