α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart

Gallego, Mónica; Setién, Raúl; Puebla, Lilian; Boyano‐Adánez, María del Carmen; Arilla, E.; Casis, Óscar

doi:10.1152/ajpcell.00124.2004

Cited by 48 publications

(41 citation statements)

References 43 publications

(50 reference statements)

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“…We performed patch-clamp experiments in freshly isolated cardiac myocytes and elicited I to current-voltage curves by applying depolarizing pulses ranging from -30 to +50 mV. As reported, 1 30 µM phenylephrine resulted in a reduction of the I to current of 32 ± 1.8% (p < 0.001). We then tested the inhibitory effect of phenylephrine on I to in the presence of the panAKAP blocker Ht31, a peptide that mimics the amphipathic helix of AKAPs that binds to the PKA, 7,8 and has been widely used as a competitive inhibitor of PKA-AKAP interactions.…”

Section: Resultsmentioning

confidence: 76%

“…1,16 The K V 4.2 channel is phosphorylated by PKA at Thr38 and Ser552. 17 However, PKA phosphorylation of the K V 4.2 is necessary but not sufficient for channel modulation.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 In our experiments K V 4.2 and K V 4.3 and reduction of I to current. 1 Membrane rafts, and particularly caveolae, have an important role in compartmentalization and modulation of a growing number of membrane-linked signal transduction pathways. Many GPCRs, G proteins and signaling molecules such as PKA, PKC or MAPK have been reported to be localized in membrane rafts (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously described that the cardiac I to current is regulated by α1-adrenoceptors (α1-AR) through a mechanism involving a Gαs protein, the subsequent activation of adenylate cyclase (AC) and finally the PKA dependent phosphorylation of the I to channel. 1 This finding, however, raises the question of how does α1-AR stimulation activate PKA without affecting i.e., L-type calcium channels. Actually, PKA is a broad-specific kinase activated by cAMP.…”

Section: Introductionmentioning

confidence: 99%

“…It is possible that the α1-AR/PKA/ I to pathway is compartmentalized and limited to specific membrane regions. In fact, the PKA dependent phosphorylation of the I to channels after α1-AR stimulation only occurs when both α1-adrenoceptors regulate only the caveolae-located subpopulation of cardiac K V 4 channels 1 Recent works demonstrate the colocalization of different receptors with their intracellular signaling cascades in discrete membrane microdomains named membrane rafts. 4 This preassembly of receptors and signaling molecules allows faster cellular responses as well as specific responses to specific stimuli.…”

Section: Introductionmentioning

confidence: 99%

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α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

Alday¹,

Urrutia²,

Gallego³

et al. 2010

Channels

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Section: Resultsmentioning

confidence: 76%

“…1,16 The K V 4.2 channel is phosphorylated by PKA at Thr38 and Ser552. 17 However, PKA phosphorylation of the K V 4.2 is necessary but not sufficient for channel modulation.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

Alday¹,

Urrutia²,

Gallego³

et al. 2010

Channels

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Signalling pathways evoked by α1-adrenoceptors in human melanoma cells

Scarparo

Visconti

Castrucci

2006

Cell Biochem. Funct.

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The biological effects of catecholamines in mammalian pigment cells are poorly understood, but in poikilothermic vertebrates they regulate the translocation of pigment granules. We have previously demonstrated in SK-Mel 23-human melanoma cells the presence of low affinity alpha(1)-adrenoceptors, which mediate a decrease in cell proliferation and increase in tyrosinase activity, with no change of tyrosinase expression. In this report, we investigated the signalling pathways involved in these responses. Calcium mobilization in response to phenylephrine (PHE), an alpha(1)-adrenergic agonist, was investigated by confocal microscopy, and no change of fluorescence during the treatment was observed, suggesting that calcium is not involved in the signalling pathway activated by alpha(1)-adrenoceptors in SK-Mel 23 cells. cAMP levels, determined by enzyme-immunoassay, were significantly increased by PHE (10(-5)-10(-4)M), that could be blocked by the alpha(1)-adrenergic antagonist benoxathian (10(-5)-10(-4)M). Several biological assays were then performed with PHE, for 72 h, in the absence or presence of various signalling pathway inhibitors, in an attempt to determine the intracellular messengers involved in the responses of proliferation and tyrosinase activity. Our results suggest the participation of p38 and ERKs in PHE-induced decrease of proliferation, and possibly also of cAMP and protein kinase A. Regarding PHE-induced increase of tyrosinase activity, it is suggested that the following signalling components are involved: cAMP/PKA, PKC, PI3K, p38 and ERKs.

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Epinephrine increases DNA synthesis via ERK1/2s through cAMP, Ca²⁺/PKC, and PI3K/Akt signaling pathways in mouse embryonic stem cells

Kim

Lee

et al. 2008

J of Cellular Biochemistry

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Epinephrine is a catecholamine that plays important roles in regulating a wide variety of physiological systems by acting through the adrenergic receptors (ARs). The cellular responses to AR stimulation are mediated through various signaling pathways. Therefore, this study examined the effects of epinephrine on DNA synthesis and related signaling molecules in mouse embryonic stem cells (ESCs). Epinephrine increased DNA synthesis in a dose- and time-dependent manner, as determined by the level of [(3)H]-thymidine incorporation. AR subtypes (alpha1(A), alpha2(A), beta1, beta2, and beta3) were expressed in mouse ESCs and their expression levels were increased by epinephrine. In this experiment, epinephrine increased cAMP levels, intracellular Ca(2+) concentration ([Ca(2+)](i)), and translocation of protein kinase C (PKC) from the cytosol to the membrane compartment. In addition, we observed Akt phosphorylation in response to epinephrine; this was stimulated by phosphorylation of the epidermal growth factor receptor (EGFR). Epinephrine also induced phosphorylation of ERK1/2 (p44/42 MAPKs), while inhibition of PKC or Akt blocked this phosphorylation. Epinephrine increased the mRNA levels of proto-oncogenes (c-fos, c-jun, c-myc), while inhibition of ERK1/2 decreased these mRNA levels. In experiments aimed at examining the involvement of cell cycle regulatory proteins, epinephrine increased the levels of cyclin E/cyclin-dependent kinase 2 (CDK2) and cyclin D1/cyclin-dependent kinase 4 (CDK4). In conclusion, epinephrine stimulates DNA synthesis via ERK1/2 through cAMP, Ca(2+)/PKC, and PI3K/Akt signaling pathways in mouse ESCs.

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α₁-Adrenoceptors stimulate a G_αs protein and reduce the transient outward K⁺ current via a cAMP/PKA-mediated pathway in the rat heart

Abstract: -Adrenoceptors stimulate a G ␣s protein and reduce the transient outward K ϩ current via a cAMP/PKA-mediated pathway in the rat heart.

Cited by 48 publications

References 43 publications

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

Signalling pathways evoked by α1-adrenoceptors in human melanoma cells

Epinephrine increases DNA synthesis via ERK1/2s through cAMP, Ca²⁺/PKC, and PI3K/Akt signaling pathways in mouse embryonic stem cells

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α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart

Abstract: -Adrenoceptors stimulate a G ␣s protein and reduce the transient outward K ϩ current via a cAMP/PKA-mediated pathway in the rat heart.

Cited by 48 publications

References 43 publications

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac KV4 channels

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac KV4 channels

Signalling pathways evoked by α1-adrenoceptors in human melanoma cells

Epinephrine increases DNA synthesis via ERK1/2s through cAMP, Ca2+/PKC, and PI3K/Akt signaling pathways in mouse embryonic stem cells

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α₁-Adrenoceptors stimulate a G_αs protein and reduce the transient outward K⁺ current via a cAMP/PKA-mediated pathway in the rat heart

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

α1-Adrenoreceptors regulate only the caveolae-located subpopulation of cardiac K_V4 channels

Epinephrine increases DNA synthesis via ERK1/2s through cAMP, Ca²⁺/PKC, and PI3K/Akt signaling pathways in mouse embryonic stem cells