cGMP/Protein Kinase G-Dependent Inhibition of N-Type Ca<sup>2+</sup>Channels Induced by Nitric Oxide in Human Neuroblastoma IMR32 Cells

D’Ascenzo, Marcello; Martinotti, Giovanni; Azzena, Gian Battista; Grassi, Claudio

doi:10.1523/jneurosci.22-17-07485.2002

Cited by 45 publications

(33 citation statements)

References 59 publications

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“…According to current literature, the role of PKG in TH activity regulation is rather controversial. It was reported that NO induces cGMP/PKG-dependent inhibition of N-type Ca 2ϩ channels in neuroblastoma cells (8). Furthermore, the NO/cGMP/PKG pathway is associated with reduced calcium entry to the cell (7,26).…”

Section: Discussionmentioning

confidence: 98%

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Perfume

Nabhen²,

Barrera³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Perfume G, Nabhen SL, Riquelme Barrera K, Otero MG, Bianciotti LG, Vatta MS. Long-term modulation of tyrosine hydroxylase activity and expression by endothelin 1 and 3 in the rat anterior and posterior hypothalamus. Am J Physiol Regul Integr Comp Physiol 294: R905-R914, 2008. First published December 19, 2007 doi:10.1152/ajpregu.00555.2007.-Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain. catecholamines; endothelin receptors; central nervous system ENDOTHELINS (ETS) ARE VASOACTIVE peptides originally isolated from cultured porcine endothelial cells (56). They constitute a family of three 21-amino acid isopeptides termed ET-1, ET-2, and ET-3 (10, 23). ETs exert their biological effects through the activation of ET A and ET B receptors that are G proteincoupled receptors (GPCRs) (10,34,38). Despite these two well pharmacologically characterized GPCRs, several pharmacological and functional studies support the existence of additional ET receptors. The finding of atypical responses in the presence of selective ET A and ET B antagonists and/or agonists observed in different studies built up the term atypical receptors (ET AX or ET BX ) to refer to those receptors that mediate ET responses but fail to be identified by using selective antagonists or agonists of the conventional ET A and ET B receptors (12,20,36,38,41). In addition, a third receptor subtype named ET C that displays high affinity for ET-3 was ...

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Section: Discussionmentioning

confidence: 98%

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Perfume

Nabhen²,

Barrera³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…NO reduces the intracellular Ca 2+ concentration in SMC by inhibiting sarcoplasmic reticulum (SR). Ca 2+ release through both IP3R and RyR [5] , and Ca 2+ influx through N-channel gating via cGMP and PKG [14] . cGMP can modulate Ca 2+ spark activity by decreasing myofibrillar Ca 2+ sensitivity and increasing Ca 2+ uptake by the SR [6] .…”

Section: Discussionmentioning

confidence: 99%

Regulation of intracellular Ca2+ and calcineurin by NO/PKG in proliferation of vascular smooth muscle cells

Sun

2005

Acta Pharmacologica Sinica

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Aim: To determine whether Ca 2+ /calcineurin mediated the inhibitory effects of nitric oxide /cGMP-dependent protein kinase (NO/PKG) on the proliferation of vascular smooth muscle cells (VSMC). Methods: Proliferation and viability of primary VSMC from rat aorta were measured using [3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] (MTT) assay and acridine orange and ethidium bromide staining, respectively. Cytosolic Ca 2+ was determined by Fluo-3/AM. Calcineurin protein and its activity were assayed using immunoblotting and free inorganic phosphate analysis, respectively. Results: (±)-S-nitroso-N-acetylpenicillamine (SNAP) and Sp-8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphorothioate (Sp-8-pCPT-cGMPS) decreased phenylephrine (PE)-induced proliferation of VSMC by 27.3% and 36.6%, respectively, but Rp-8-[(4-chlorophenyl)thio]-guanosine-3',5'-cyclic monophosphorothioate (Rp-8-pCPTcGMPS) increased PE-induced proliferation of VSMC. SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT-cGMPS did not affect the viability of VSMC. Calcineurin protein was decreased by 63.1% and its activity was decreased by 59.7% in smooth muscle cells (SMC) pretreated with verapamil (Ver) and then stimulated by PE. In SMC pretreated with Ver, the absorbance of cells stimulated by PE decreased by 22.0% and was further inhibited by the additional treatment of SNAP and Sp-8-pCPTcGMPS. In SMC pretreated with cyclosporin A (CsA), the absorbance of cells stimulated by PE decreased by 36.7%, but could not be further altered by the additional treatment of SNAP, Sp-8-pCPT-cGMPS, and Rp-8-pCPT-cGMPS. In addition, Ver inhibited PE-induced intracellular Ca 2+ variations, which could be further inhibited by SNAP and Sp-8-pCPT-cGMPS, but not by Rp-8-pCPT-cGMPS. Moreover, the increase in calcineurin activity induced by PE was inhibited by SNAP and Sp-8-pCPT-cGMPS, but was promoted by Rp-8-pCPT-cGMPS. Conclusion: NO/PKG regulates calcineurin activity via the modulation of intracellular Ca 2+ concentration, and thus partially inhibits the proliferation of VSMC without affecting their viability.

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“…In the vestibular system of the chinchilla and rat, NADPH-d histochemistry and NOS-I positive immunoreactivity were found in a subpopulation of vestibular-efferent neurons contacting hair cells (Lysakowski and Singer 2000). NOS-I, calretinin, and sGC were co-localized in calyx-ending afferent neurons of the chinchilla and both sGC and calmodulin, an important cofactor of NOS (Bredt 1999), were co-localized in type I and type II hair cells (Desai et al 2004;Dhaliwal and Lysakowski 2000). NOS was colocalized with sGC and cGMP in the sensory epithelia and the vestibular nerve fibers of the guinea pig and mice (Hess et al 1998a,b).…”

Section: Introductionmentioning

confidence: 99%

Modulation of Voltage-Gated Ca²⁺Current in Vestibular Hair Cells by Nitric Oxide

Almanza¹,

Navarrete²,

Vega³

et al. 2007

Journal of Neurophysiology

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Almanza A, Navarrete F, Vega R, Soto E. Modulation of voltagegated Ca 2ϩ current in vestibular hair cells by nitric oxide. J Neurophysiol 97: 1188Neurophysiol 97: -1195Neurophysiol 97: , 2007. First published December 20, 2006; doi:10.1152/jn.00849.2006. The structural elements of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway have been described in the vestibular peripheral system. However, the functions of NO in the vestibular endorgans are still not clear. We evaluated the action of NO on the Ca 2ϩ currents in hair cells isolated from the semicircular canal crista ampullaris of the rat (P14 -P18) by using the whole cell and perforated-cell patch-clamp technique. The NO donors 3-morpholinosydnonimine (SIN-1), sodium nitroprusside (SNP), and ( In the presence of Nethylmaleimide (NEM), a sulfhydryl alkylating agent that prevents the S-nitrosylation reaction, the SNP effect on the Ca 2ϩ current was significantly diminished. These results demonstrated that NO inhibits in a voltage-independent manner the voltage-activated Ca 2ϩ current in rat vestibular hair cells by the activation of a cGMP-signaling pathway and through a direct action on the channel protein by a Snitrosylation reaction. The inhibition of the Ca 2ϩ current by NO may contribute to the regulation of the intracellular Ca 2ϩ concentration and hair-cell synaptic transmission.

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cGMP/Protein Kinase G-Dependent Inhibition of N-Type Ca²⁺Channels Induced by Nitric Oxide in Human Neuroblastoma IMR32 Cells

Cited by 45 publications

References 59 publications

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Regulation of intracellular Ca2+ and calcineurin by NO/PKG in proliferation of vascular smooth muscle cells

Modulation of Voltage-Gated Ca²⁺Current in Vestibular Hair Cells by Nitric Oxide

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cGMP/Protein Kinase G-Dependent Inhibition of N-Type Ca2+Channels Induced by Nitric Oxide in Human Neuroblastoma IMR32 Cells

Cited by 45 publications

References 59 publications

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Regulation of intracellular Ca2+ and calcineurin by NO/PKG in proliferation of vascular smooth muscle cells

Modulation of Voltage-Gated Ca2+Current in Vestibular Hair Cells by Nitric Oxide

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cGMP/Protein Kinase G-Dependent Inhibition of N-Type Ca²⁺Channels Induced by Nitric Oxide in Human Neuroblastoma IMR32 Cells

Modulation of Voltage-Gated Ca²⁺Current in Vestibular Hair Cells by Nitric Oxide