Differential Coupling of α1-, α2-, and β-Adrenergic Receptors to Mitogen-activated Protein Kinase Pathways and Differentiation in Transfected PC12 Cells

Williams, Nidhi Gupta; Zhong, Hongying; Minneman, Kenneth P.

doi:10.1074/jbc.273.38.24624

Cited by 100 publications

(93 citation statements)

References 58 publications

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“…When ␣ 2 receptors were ectopically expressed in Rat-1 cells (7), in HEK-293 cells (19) or in 3T3-F442A (39,40), adrenergic stimulation caused Erk1/2 activation, and pertussis toxin totally blocked the activation. However, the inability of ␣ 2 receptors to activate Erk1/2 in brown adipocytes is in agreement with observations in another non-fibroblast cell line, PC12 cells (34).…”

Section: Discussionsupporting

confidence: 78%

“…Also ␣ 1 -induced Erk1/2 activation was mediated in a G i -independent manner, confirming the nonessentially of this mediator protein for Erk1/2 activation (although such an ␣ 1 -pathway has been described in primary hepatocytes (32)). An ability of G i to activate Erk1/2 has been observed in several other systems (7-9, 32), although a noninvolvement of G i in the mediation has also been reported in other G-protein-coupled systems (33,34).…”

Section: Discussionmentioning

confidence: 98%

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β3- and α1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes

Lindquist

Fredriksson

Rehnmark

et al. 2000

Journal of Biological Chemistry

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A novel signaling pathway for mediation of ␤ 3 -adrenergic activation of the mitogen-activated protein kinases Erk1/2 (associated with proliferation, differentiation, and apoptosis) has recently been proposed, which implies mediation via constitutively coupled G i -proteins and G␤␥-subunits, distinct from the classical cAMP pathway of ␤-adrenergic stimulation. To verify the significance of this pathway in cells in primary cultures that entopically express ␤ 3 -adrenoreceptors, we examined the functionality of this pathway in cultured brown adipocytes. Norepinephrine activated Erk1/2 via both ␤ 3 receptors and ␣ 1 receptors but not via ␣ 2 receptors. Forskolin induced Erk1/2 activation similarly to ␤ 3 activation, indicating cAMP-mediation; this induction could be inhibited with H89, implying protein kinase A mediation. The G i -pathway was functional in these cells, as pertussis toxin increased agonist-induced cAMP accumulation. However, pertussis toxin was unable to affect adrenergically induced Erk1/2 activation. Also, wortmannin was without effect, implying that G␤␥ activation of the phosphatidylinositol 3-kinase pathway was not involved. PP1/2, which inhibits Src, abolished both ␤ 3 -and ␣ 1 -induced Erk1/2 activation. Thus, the proposed novel G i pathway for ␤ 3 mediation is not universal, because it is not functional in the untransformed primary cell culture system with entopically expressed ␤ 3 receptors examined here. Here, the ␤ 3 signal is mediated classically via cAMP/protein kinase A. ␤ 3 and ␣ 1 signals converge at Src, which thus mediates Erk1/2 activation in both pathways.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 98%

β3- and α1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes

Lindquist

Fredriksson

Rehnmark

et al. 2000

Journal of Biological Chemistry

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“…Ligands for adrenergic receptors usually activate ERK1/2 in cells other than ␤-cells (29 -31). ␣ 2 -adrenergic receptors are not coupled to ERK1/2 activation in PC12 cells, suggesting that neuroendocrine cells may be exceptions (32).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Glucose-Stimulated Activation of Extracellular Signal–Regulated Protein Kinases 1 and 2 by Epinephrine in Pancreatic β-Cells

et al. 2006

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Glucose sensing is essential for the ability of pancreatic ␤-cells to produce insulin in sufficient quantities to maintain blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose by promoting glucose production and inhibiting insulin release. We have shown that extracellular signalregulated kinases 1 and 2 (ERK1/2) are responsive to glucose in pancreatic ␤-cells and that glucose activates ERK1/2 by mechanisms independent of insulin. Here we show that glucose-induced activation of ERK1/2 is inhibited by epinephrine through the ␣ 2 -adrenergic receptor. Epinephrine and the selective ␣ 2 -adrenergic agonist UK14304 reduced insulin secretion and glucose-stimulated ERK1/2 activation in a pertussis toxin-sensitive manner, implicating the ␣ subunit of a Gi family member. ␣ 2 -adrenergic agonists also reduced stimulation of ERK1/2 by glucagon-like peptide 1 and KCl, but not by phorbol ester or nerve growth factor. Our findings suggest that ␣ 2 -adrenergic agonists act via a Gi family member on early steps in ERK1/2 activation, supporting the idea that ERK1/2 are regulated in a manner that reflects insulin demand.

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“…It has been proposed that these receptors trigger similar changes in the CNS during successful adaptation to chronic stress and antidepressant therapy to yield adaptive changes in neural output or plasticity brought about by actions of growth factors (Stone, 1983;Duman et al, 1999Duman et al, , 2000. In support of this, a 1 -receptor activation has been shown to stimulate both the expression of immediate early genes in the cortex, limbic system and brainstem during stress (Bing et al, 1991;Stone and Zhang, 1995) as well as the phosphorylation of cortical MAPK (Williams et al, 1998), which is involved in growth factor signaling processes. As noted above, in preliminary experiments, modafinil has been found to activate MAPK in cell culture as well as in vivo in the mouse cerebral cortex and to do so via stimulation of a 1 -receptors.…”

Section: Trophic Actions Of a 1 -Receptorsmentioning

confidence: 96%

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

Stone

Yang

Rosengarten

et al. 2003

Neuropsychopharmacol

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Currently, most basic and clinical research on depression is focused on either central serotonergic, noradrenergic, or dopaminergic neurotransmission as affected by various etiological and predisposing factors. Recent evidence suggests that there is another system that consists of a subset of brain a 1B -adrenoceptors innervated primarily by brain epinephrine (EPI) that potentially modulates the above three monoamine systems in parallel and plays a critical role in depression. The present review covers the evidence for this system and includes findings that brain a 1 -adrenoceptors are instrumental in behavioral activation, are located near the major monoamine cell groups or target areas, receive EPI as their neurotransmitter, are impaired or inhibited in depressed patients or after stress in animal models, and are restored by a number of antidepressants. This 'EPI-a 1 system' may therefore represent a new target system for this disorder.

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Differential Coupling of α1-, α2-, and β-Adrenergic Receptors to Mitogen-activated Protein Kinase Pathways and Differentiation in Transfected PC12 Cells

Cited by 100 publications

References 58 publications

β3- and α1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes

β3- and α1-Adrenergic Erk1/2 Activation Is Src- but Not Gi-mediated in Brown Adipocytes

Inhibition of Glucose-Stimulated Activation of Extracellular Signal–Regulated Protein Kinases 1 and 2 by Epinephrine in Pancreatic β-Cells

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

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