Pituitary Adenylate Cyclase-Activating Polypeptide Enhances Ca2+-Dependent Neurotransmitter Release from PC12 Cells and Cultured Cerebellar Granule Cells without Affecting Intracellular Ca2+ Mobilization

Aoyagi, Kyota; Takahashi, Masami

doi:10.1006/bbrc.2001.5443

Cited by 18 publications

(3 citation statements)

References 31 publications

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“…In this model, PACAP can either induce transient calcium mobilization (Dziema and Obrietan, 2002) or increase the amplitude and/or frequency of spontaneous calcium spikes (Michel et al, 2006). In cultured granule cells, some studies report that PACAP fails to increase calcium levels (Aoyagi and Takahashi, 2001) while others indicate that PACAP induces calcium mobilization (Mei, 1999). In cerebellar tissue slices, PACAP has no effect on the frequency of calcium transients but decreases the amplitude of calcium oscillations in granule cells (Cameron et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels

Basille-Dugay¹,

Vaudry²,

Fournier³

et al. 2013

Front. Endocrinol.

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High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) and a high density of PACAP binding sites have been detected in the developing rat cerebellum. In particular, PACAP receptors are actively expressed in immature granule cells, where they activate both adenylyl cyclase and phospholipase C. The aim of the present study was to investigate the ability of PACAP to induce calcium mobilization in cerebellar granule neurons. Administration of PACAP-induced a transient, rapid, and monophasic rise of the cytosolic calcium concentration ([Ca2+]i), while vasoactive intestinal peptide was devoid of effect, indicating the involvement of the PAC1 receptor in the Ca2+ response. Preincubation of granule cells with the Ca2+ ATPase inhibitor, thapsigargin, or the d-myo-inositol 1,4,5-trisphosphate (IP3) receptor antagonist, 2-aminoethoxydiphenyl borate, markedly reduced the stimulatory effect of PACAP on [Ca2+]i. Furthermore, addition of the calcium chelator, EGTA, or exposure of cells to the non-selective Ca2+ channel blocker, NiCl2, significantly attenuated the PACAP-evoked [Ca2+]i increase. Preincubation of granule neurons with the N-type Ca2+ channel blocker, ω-conotoxin GVIA, decreased the PACAP-induced [Ca2+]i response, whereas the L-type Ca2+ channel blocker, nifedipine, and the P- and Q-type Ca2+ channel blocker, ω-conotoxin MVIIC, had no effect. Altogether, these findings indicate that PACAP, acting through PAC1 receptors, provokes an increase in [Ca2+]i in granule neurons, which is mediated by both mobilization of calcium from IP3-sensitive intracellular stores and activation of N-type Ca2+ channel. Some of the activities of PACAP on proliferation, survival, migration, and differentiation of cerebellar granule cells could thus be mediated, at least in part, through these intracellular and/or extracellular calcium fluxes.

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Section: Introductionmentioning

confidence: 99%

Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels

Basille-Dugay¹,

Vaudry²,

Fournier³

et al. 2013

Front. Endocrinol.

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“…This new pathway may facilitate the maturation of granule precursors into excitable neurons. In support of this notion, PACAP has been shown to enhance the release of glutamate induced by granule cell depolarization [31]. The antimitotic effect of PACAP can also be associated with its prodifferentiating activity.…”

Section: Effects Of Pacap On Granule Cell Differentiationmentioning

confidence: 92%

Neurotrophic Effects of PACAP in the Cerebellar Cortex

Falluel‐Morel

Vaudry

Komuro

et al. 2011

Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was originally isolated from the ovine hypothalamus on the basis of its ability to stimulate cAMP formation in rat anterior pituitary cells [1]. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-GHRH-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution, which suggests that the peptide should be involved in the regulation of important biological functions [2]. PACAP acts through three distinct receptors named PAC1-R, VPAC1-R, and VPAC2-R. PACAP has a much higher affinity than VIP for PAC1-R while both peptides bind similarly to VPAC1-R and VPAC2-R. All three receptors are positively coupled to the adenylyl cyclase, but PAC1-R also stimulates the phospholipase C (PLC) and the extracellular regulated kinase (ERK) pathways [3]. PAC1-R has several variants that result mainly from the alternative splicing of the mRNA regions encoding the first extracellular domain and the third intracellular cytoplasmic loop [4], which are coupled to differential transduction mechanisms. For instance, both the short and hop variants strongly activate the protein kinase A (PKA) and PLC pathways, whereas the hip isoform does not signal through the PLC pathway at all [5]. In addition, the hip/hop form displays an intermediate phenotype with a reduced ability to activate both signal transduction pathways [5].PACAP and its receptors are widely distributed in the brain and peripheral organs, and the peptide has been found to exert pleiotropic effects on hormone secretion, vasodilation, regulation of inflammation, and apoptosis [3]. Besides, increasing evidence indicates that PACAP exerts neurotrophic actions during development and neuroprotective activities in the adult brain. Here, we review the current knowledge regarding the role of PACAP during histogenesis of the cerebellar cortex. Expression of PACAP and its Receptors in the Developing CerebellumIn the brain, the highest concentrations of PACAP are found in the hypothalamus and cerebellum [6]. PACAP is detected in the rat brain as early as embryonic day 14

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“…Depolarization-induced dopamine release and intracellular dopamine content were quantified as described previously (Aoyagi and Takahashi, 2001). Cells cultured in 60-mm plastic dishes were rinsed three times with normal bath solution containing 140 mM NaCl, 5 mM KCl, 2 mM CaCl 2 , 1 mM MgCl 2 , 10 mM d-glucose, 1 mg/ml BSA and 10 mM HEPES-Na at pH 7.4, and incubated in 1.4 ml of normal bath solution or high potassium bath solution for 15 min at room temperature.…”

Section: Dopamine Assaymentioning

confidence: 99%

Serum-free culture conditions for serial subculture of undifferentiated PC12 cells

Ohnuma

Hayashi

Furue

et al. 2006

Journal of Neuroscience Methods

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Pituitary Adenylate Cyclase-Activating Polypeptide Enhances Ca2+-Dependent Neurotransmitter Release from PC12 Cells and Cultured Cerebellar Granule Cells without Affecting Intracellular Ca2+ Mobilization

Cited by 18 publications

References 31 publications

Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels

Activation of PAC1 Receptors in Rat Cerebellar Granule Cells Stimulates Both Calcium Mobilization from Intracellular Stores and Calcium Influx through N-Type Calcium Channels

Neurotrophic Effects of PACAP in the Cerebellar Cortex

Serum-free culture conditions for serial subculture of undifferentiated PC12 cells

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