Analysis of Regulated Secretion Using PC12 Cells

Taupenot, Laurent

doi:10.1002/0471143030.cb1512s36

Cited by 15 publications

(15 citation statements)

References 11 publications

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“…This, in fact, suggested that H 3 Rs may influence neuronal AT 1 R expression in hearts subjected to I/R. Inasmuch as cardiac synaptosomes probably include cholinergic, purinergic, and sensory C-fiber terminals (Seyedi et al, 1999;Morrey et al, 2010), we tested whether H 3 R activation would influence AT 1 R expression in PC12-H 3 cells, which once differentiated with NGF express a typical sympathetic neuron phenotype (Taupenot, 2007;Morrey et al, 2008;Corti et al, 2011). Indeed, we found that activation of H 3 R with imetit markedly diminished AT 1 R protein abundance in these cells, an action that was abolished by the H 3 R antagonist clobenpropit.…”

Section: Discussionmentioning

confidence: 99%

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Hashikawa-Hobara¹,

Chan²,

Levi³

2011

J Pharmacol Exp Ther

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In severe myocardial ischemia, histamine 3 (H 3 ) receptor activation affords cardioprotection by preventing excessive norepinephrine release and arrhythmias; pivotal to this action is the inhibition of neuronal Na ϩ /H ϩ exchanger (NHE). Conversely, angiotensin II, formed locally by mast cell-derived renin, stimulates NHE via angiotensin II type 1 (AT 1 ) receptors, facilitating norepinephrine release and arrhythmias. Thus, ischemic dysfunction may depend on a balance between the NHE-modulating effects of H 3 receptors and AT 1 receptors. The purpose of this investigation was therefore to elucidate the H 3 /AT 1 receptor interaction in myocardial ischemia/reperfusion. We found that H 3 receptor blockade with clobenpropit increased norepinephrine overflow and arrhythmias in Langendorff-perfused guinea pig hearts subjected to ischemia/reperfusion. This coincided with increased neuronal AT 1 receptor expression. NHE inhibition with cariporide prevented both increases in norepinephrine release and AT 1 receptor expression. Moreover, norepinephrine release and AT 1 receptor expression were increased by the nitric oxide (NO) synthase inhibitor N G -methyl-L-arginine and the protein kinase C activator phorbol myristate acetate. H 3 receptor activation in differentiated sympathetic neuron-like PC12 cells permanently transfected with H 3 receptor cDNA caused a decrease in protein kinase C activity and AT 1 receptor protein abundance. Collectively, our findings suggest that neuronal H 3 receptor activation inhibits NHE by diminishing protein kinase C activity. Reduced NHE activity sequentially causes intracellular acidification, increased NO synthesis, and diminished AT 1 receptor expression. Thus, H 3 receptor-mediated NHE inhibition in ischemia/reperfusion not only opposes the angiotensin II-induced stimulation of NHE in cardiac sympathetic neurons, but also down-regulates AT 1 receptor expression. Cardioprotection ultimately results from the combined attenuation of angiotensin II and norepinephrine effects and alleviation of arrhythmias.

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Section: Discussionmentioning

confidence: 99%

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Hashikawa-Hobara¹,

Chan²,

Levi³

2011

J Pharmacol Exp Ther

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“…After preincubation, cells were incubated for 3 h in the same medium ("3 h basal") followed by 15-min incubations without ("ϪK") and with ("ϩK") 55 mM KCl to stimulate granule exocytosis (35). Cells were quickly rinsed in Hanks' buffered salt solution between incubations.…”

Section: Methodsmentioning

confidence: 99%

Two Dipolar α-Helices within Hormone-encoding Regions of Proglucagon Are Sorting Signals to the Regulated Secretory Pathway

Guizzetti¹,

McGirr

Dhanvantari

2014

Journal of Biological Chemistry

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Background:The constituent peptides of proglucagon contain ␣-helices that may target proglucagon to secretory granules. Results: Sorting of proglucagon processing intermediates is context-dependent, despite containing two sorted domains of glucagon and glucagon-like peptide 1. Conclusion: Proglucagon sorting is directed by two dipolar ␣-helices within glucagon and GLP-1. Significance: Hormone domains, rather than disordered prodomains, encode proglucagon sorting signals.

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“…In our investigation, we used the PC12 rat pheochromocytoma cell line, which acquires a sympathetic nerve phenotype when treated with NGF (Dichter et al, 1977;Taupenot, 2007). Having stably transfected PC12 cells with human H 3 R, a PTX-sensitive G i/o -coupled receptor (see Figs.…”

Section: Discussionmentioning

confidence: 99%

“…To accomplish this, we evaluated the effects of H 3 R activation on I Ca and endogenous transmitter exocytosis in nerve-growth factor (NGF)-differentiated rat pheochromocytoma cells (PC12) stably transfected with H 3 R and the G␤␥ scavenger ␤-adrenergic receptor kinase 1 (␤-ARK1)-(495-689)-polypeptide (Koch et al, 1994;Dickenson and Hill, 1998). NGF-differentiated PC12 cells were chosen as a functional model of sympathetic neurotransmission because their phenotype closely resembles that of sympathetic neurons (Dichter et al, 1977;Taupenot, 2007). Our results demonstrate a pivotal involvement of the G␤␥ subunit in H 3 R-mediated attenuation of neuronal I Ca and consequent neurotransmitter exocytosis.…”

mentioning

confidence: 99%

Cardioprotective Effect of Histamine H₃-Receptor Activation: Pivotal Role of Gβγ-Dependent Inhibition of Voltage-Operated Ca²⁺Channels

Morrey¹,

Estephan²,

Abbott³

et al. 2008

J Pharmacol Exp Ther

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We previously showed that activation of G i/o -coupled histamine H 3 -receptors (H 3 R) is cardioprotective because it attenuates excessive norepinephrine release from cardiac sympathetic nerves. This action is characterized by a marked decrease in intraneuronal Ca 2ϩ ([Ca 2ϩ ] i ), as G␣ i impairs the adenylyl cyclasecAMP-protein kinase A (PKA) pathway, and this decreases Ca 2ϩ influx via voltage-operated Ca 2ϩ channels (VOCC). Yet, the G i/oderived ␤␥ dimer could directly inhibit VOCC, and the subsequent reduction in Ca 2ϩ influx would be responsible for the H 3 Rmediated attenuation of transmitter exocytosis. In this study, we tested this hypothesis in nerve-growth factor-differentiated rat pheochromocytoma cells (PC12) stably transfected with H 3 R (PC12-H 3 ) and with the G␤␥ scavenger ␤-adrenergic receptor kinase 1 (␤-ARK1)-(495-689)-polypeptide (PC12-H 3 /␤-ARK1). Thus, we evaluated the effects of H 3 R activation directly on the following: 1) Ca 2ϩ current (I Ca ) using the whole-cell patchclamp technique; and 2) K ϩ -induced exocytosis of endogenous dopamine. H 3 R activation attenuated both peak I Ca and dopamine exocytosis in PC12-H 3 but not in PC12-H 3 /␤-ARK1 cells. Moreover, a membrane permeable phosducin-like G␤␥ scavenger also prevented the antiexocytotic effect of H 3 R activation. In contrast, the H 3 R-induced attenuation of cAMP accumulation and dopamine exocytosis in response to forskolin were the same in both PC12-H 3 and PC12-H 3 /␤-ARK1 cells. Our findings reveal that although G␣ i participates in the H 3 -mediated antiexocytotic effect when the adenylyl cyclase-cAMP-PKA pathway is stimulated, a direct G␤␥-induced inhibition of VOCC, resulting in an attenuation of I Ca , plays a pivotal role in the H 3 R-mediated decrease in [Ca 2ϩ ] i and associated cardioprotective antiexocytotic effects. The discovery of this H 3 R-signaling step may offer new therapeutic approaches to cardiovascular diseases characterized by hyperadrenergic activity.

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Analysis of Regulated Secretion Using PC12 Cells

Cited by 15 publications

References 11 publications

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Two Dipolar α-Helices within Hormone-encoding Regions of Proglucagon Are Sorting Signals to the Regulated Secretory Pathway

Cardioprotective Effect of Histamine H₃-Receptor Activation: Pivotal Role of Gβγ-Dependent Inhibition of Voltage-Operated Ca²⁺Channels

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Analysis of Regulated Secretion Using PC12 Cells

Cited by 15 publications

References 11 publications

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Histamine 3 Receptor Activation Reduces the Expression of Neuronal Angiotensin II Type 1 Receptors in the Heart

Two Dipolar α-Helices within Hormone-encoding Regions of Proglucagon Are Sorting Signals to the Regulated Secretory Pathway

Cardioprotective Effect of Histamine H3-Receptor Activation: Pivotal Role of Gβγ-Dependent Inhibition of Voltage-Operated Ca2+Channels

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Cardioprotective Effect of Histamine H₃-Receptor Activation: Pivotal Role of Gβγ-Dependent Inhibition of Voltage-Operated Ca²⁺Channels