A new phospholipase-C–calcium signalling pathway mediated by cyclic AMP and a Rap GTPase

Schmidt, Martina; Evellin, Sandrine; Weernink, Paschal A. Oude; Dorp, F. vom; Rehmann, Holger; Lomasney, Jon W.; Jakobs, Karl H.

doi:10.1038/ncb1101-1020

Cited by 303 publications

(307 citation statements)

References 32 publications

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“…Less extensive but consistent findings lead to a similar conclusion regarding the Rap exchange factor Epac. Despite that cAMP effectors play important roles in ␤-cell function (23,(33)(34)(35)(36), the cumulative results suggest that these cAMP effectors are not direct mediators of glucose signaling to ERK1/2 in ␤-cells.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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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“…It has been proposed that epinephrine, acting on nociceptors, produces mechanical hyperalgesia through three different signaling pathways involving 1) cAMP-dependent PKA; 2) epsilon isozyme of PKC; and 3) extracellular signal-regulated kinases 1 and 2 (1,20). It has been demonstrated that the latter two pathways may also be initiated by the accumulation of cAMP (8,35). However, recent pharmacological and electrophysiological studies have reported the presence of ␤-adrenoceptor-mediated cAMP-independent signaling pathways (38); for example, the ␤ 3 -adrenoceptor-induced relaxation of gastrointestinal smooth muscle has been proposed to be mediated through the activation of a delayed rectified K ϩ channel (15).…”

Section: Discussionmentioning

confidence: 99%

Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β₃-adrenoceptor

Lin

Lee

2007

Journal of Applied Physiology

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Gu Q, Lin Y-S, Lee L-Y. Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of ␤3-adrenoceptor. J Appl Physiol 102: [1545][1546][1547][1548][1549][1550][1551][1552][1553][1554][1555] 2007. First published December 14, 2006; doi:10.1152/japplphysiol.01010.2006.-This study was carried out to determine whether epinephrine alters the sensitivity of rat vagal sensory neurons. In anesthetized rats, inhalation of epinephrine aerosol (1 and 5 mg/ml, 3 min) induced an elevated baseline activity of pulmonary C fibers and enhanced their responses to lung inflation (20 cmH 2O, 10 s) and right atrial injection of capsaicin (0.5 g/kg). In isolated rat nodose and jugular ganglion neurons, perfusion of epinephrine (3 M, 5 min) alone did not produce any detectable change of the intracellular Ca 2ϩ concentration. However, immediately after the pretreatment with epinephrine, the Ca 2ϩ transients evoked by chemical stimulants (capsaicin, KCl, and ATP) were markedly potentiated; for example, capsaicin (50 nM, 15 s)-evoked Ca 2ϩ transient was increased by 106% after epinephrine (P Ͻ 0.05; n ϭ 11). The effect of epinephrine was mimicked by either BRL 37344 (5 M, 5 min) or ICI 215,001 (5 M, 5 min), two selective ␤ 3-adrenoceptor agonists, and blocked by SR 59230A (5 M, 10 min), a selective ␤ 3-adrenoceptor antagonist, whereas pretreatment with phenylephrine (␣ 1-adenoceptor agonist), guanabenz (␣2-adrenoceptor agonist), dobutamine (␤ 1-adrenoceptor agonist), or salbutamol (␤2-adrenoceptor agonist) had no significant effect on capsaicin-evoked Ca 2ϩ transient. Furthermore, pretreatment with SQ 22536 (100 -300 M, 15 min), an adenylate cyclase inhibitor, and H89 (3 M, 15 min), a PKA inhibitor, completely abolished the potentiating effect of epinephrine. Our results suggest that epinephrine enhances the excitability of rat vagal chemosensitive neurons. This sensitizing effect of epinephrine is likely mediated through the activation of ␤ 3-adrenoceptor and intracellular cAMP-PKA signaling cascade. stress; vagal afferents; fura-2; adenylate cyclase; cAMP-dependent protein kinase EPINEPHRINE IS THE PRIMARY CATECHOLAMINE secreted by the adrenal medulla in response to various physiological stresses (41). The physiological functions of epinephrine are mediated through the activation of cell membrane ␣-and ␤-adrenoceptors, both of which belong to the superfamily of seven-transmembrane G-protein-coupled receptors (13). Vagus nerves provide the primary afferent innervation of a broad spectrum of visceral organs and play an important role in the initiation of visceral/viscerosomatic reflexes and the regulation of vegetative functions (24,29). Numerous studies have identified the presence of ␤-adrenoceptors on the vagus nerve in both rats and humans (23,28). Although a sensitizing effect of epinephrine on nociceptors was recently reported (21), whether epinephrine can modulate the excitability of vagal sensory neurons is largely unknown.The aims of the present study were 1) to determine whether epinephrine alters the excit...

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“…While the independent studies of PLCe corresponding to PLCe1a and PLCe1b demonstrated some similarities, they also pointed out potential differences in the type of agonist capable of PLCe stimulation (Evellin et al, 2002;Schmidt et al, 2001;Kelley et al, 2004). In addition, significant differences could exist regarding the ability of H-Ras to stimulate these two forms Lopez et al, 2001).…”

Section: Signaling Properties and Subcellular Localization Of Plce1a mentioning

confidence: 99%

“…In some of the studies, it was also shown that PI-PLC activity of PLCe can be stimulated by activated Ras when both molecules were introduced into COS cells Song et al, 2002). An increase in substrate hydrolysis by PLCe in transfected cells have been observed after stimulation by diverse stimuli including epidermal growth factor (EGF), lysophosphatic acid (LPA), sphingosine-1-phosphate (S1P), adrenalin and acetycholine (Schmidt et al, 2001;Evellin et al, 2002;Kelley et al, 2004). Furthermore, these and other studies suggest that signaling pathways triggered by these agonists could be quite broad and in some cases independent of Ras family GTP-ases (Lopez et al, 2001;Wing et al, 2001Wing et al, , 2003Kelley et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants

et al. 2004

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Phospholipase Ce (PLCe) is a novel member of phosphoinositide-specific phospholipase C enzymes with a unique regulatory link to Ras GTP-ases. In the present studies, we establish existence of two splice variants (PLCe1a and PLCe1b) derived from human PLCe1 gene. When expressed in COS or HEK293 cells, PLCe1a and PLCe1b have similar potential to be stimulated by diverse signaling pathways via tyrosine kinase and G-protein coupled receptors and share the ability to function as an effector of Ras. The expression pattern shows broader mRNA expression of PLCe1a in normal tissues; furthermore, in most cell lines expressing PLCe, PLCe1a is the only splice variant present. Analysis of normal/tumor matched pairs derived from colon and rectum demonstrates greatly reduced expression levels in tumor tissues. Further studies in a colorectal tumor cell line lacking PLCe show restoration of transcription of PLCe1a and PLCe1b by demethylating agent 5-aza-2 0 -deoxycytidine, suggesting epigenetic silencing through hypermethylation. In addition, expression of exogenous PLCe in this cell line demonstrates inhibitory effects of PLCe on cell viability and proliferation. Taken together, our findings suggest that regulatory mechanisms controlling expression of PLCe, broadened by diversity introduced by splice variants, could play important role in PLCe regulation in normal and tumor cells.

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A new phospholipase-C–calcium signalling pathway mediated by cyclic AMP and a Rap GTPase

Cited by 303 publications

References 32 publications

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

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

Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β₃-adrenoceptor

Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants

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A new phospholipase-C–calcium signalling pathway mediated by cyclic AMP and a Rap GTPase

Cited by 303 publications

References 32 publications

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

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

Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β3-adrenoceptor

Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants

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Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of β₃-adrenoceptor