Inhibition of phospholipase C-ε by Gi-coupled receptors

Dorp, F. vom; Sari, Aysegül Y; Sanders, Harald; Keiper, Melanie; Weernink, Paschal A. Oude; Jakobs, Karl H.; Schmidt, Martina

doi:10.1016/j.cellsig.2004.01.009

Cited by 17 publications

(11 citation statements)

References 24 publications

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“…The increased PGE 2 release may be related to cross-talk among the second messenger systems activated by G q , G i , and/or G s protein-coupled receptors. Activation of G i -coupled receptors has been shown to affect PLC and/or PKC activity either directly or via inhibition of the AC/cAMP transduction pathway in neuronal and nonneuronal cells (1,28,38,47). The relevance of these findings to the current studies relates to our previous studies, showing that activation of renal mechanosensory nerves involves activation of the PKC and cAMP/PKA transduction cascades (16,23).…”

Section: Interaction Between Ersna and Arnasupporting

confidence: 73%

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Kopp

Cicha

Smith

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α(1)-and α(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.

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Section: Interaction Between Ersna and Arnasupporting

confidence: 73%

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Kopp

Cicha

Smith

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Therefore, we first examined whether Rap2B is also involved in H-Ras and ERK activation by the ␤ 2 -AR. As reported before (31,41) and shown in Fig. 6, A and B, activation of the ␤ 2 -AR by adrenaline (10 M) or stimulation of the cells with forskolin (30 M) or 8-pCPT-2Me-cAMP (10 M) induced GTP loading of Rap2B.…”

Section: Epac-and Ca 2ϩ -Controlled Ras and Erk Activation 46500mentioning

confidence: 60%

“…Third, receptor-mediated H-Ras and ERK activation was apparently dependent on stimulation of Rap2B-activated PLC-⑀ (31,35). We very recently reported that not only G s -coupled receptors but also stimulation of HEK-293 cells and N1E-115 neuroblastoma cells with 8-pCPT-2Me-cAMP or expression of constitutively active Rap2B results in marked PLC-⑀ stimulation (41). As expression of lipase-inactive H1144L PLC-⑀ suppressed ␤ 2 -AR-mediated H-Ras and ERK activation, whereas overexpression of wild-type PLC-⑀ had the opposite effect, it can be concluded that the lipase activity of the Rap2B-activated PLC-⑀ is required for H-Ras and ERK activation.…”

Section: Epac-and Ca 2ϩ -Controlled Ras and Erk Activation 46505mentioning

confidence: 99%

Epac- and Ca2+-controlled Activation of Ras and Extracellular Signal-regulated Kinases by Gs-coupled Receptors

Keiper¹,

Stope²,

Szatkowski

et al. 2004

Journal of Biological Chemistry

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101

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We have recently reported that two typical G s -coupled receptors, the ␤ 2 -adrenergic receptor and the receptor for prostaglandin E 1 , stimulate phospholipase C-⑀ (PLC- Activation of mitogen-activated protein (MAP) 1 kinases plays a prominent role in many cellular responses to a large variety of membrane receptors. Initially identified as signal transducers of growth factor receptors with intrinsic tyrosine kinase activity, activation of MAP kinases, specifically of the extracellular signal-regulated kinases 1 and 2 (ERK1/2), is now also recognized as a major signal transduction pathway of many receptors coupled to heterotrimeric G proteins. ERK activation by these second messenger-generating receptors is apparently accomplished by diverse molecular mechanisms, depending on the cell types studied as well as the receptor and the heterotrimeric G protein involved (1-5).⑀The cAMP-producing G s -coupled receptors play a rather unique role in ERK activation. These receptors inhibit ERK activation by growth factor receptors in several cell types while stimulating this cellular response in others, most notably in neuronal and endocrine cells. Several models have been proposed to explain these diverse actions of cAMP and G s -coupled receptors on ERK activation, both apparently involving in most cases the principal cAMP target, the cAMP-activated protein kinase (PKA) (6, 7). In particular, PKA-dependent ERK activation in HEK-293 cells by the ␤ 2 -adrenergic receptor (␤ 2 -AR), a prototypical G s -coupled receptor, has been extensively studied. Lefkowitz and coworkers (8) reported that cAMP-activated PKA phosphorylates the ␤ 2 -AR and thereby alters the coupling specificity of the receptor from G s to G i proteins. By this G protein "switching," the ␤ 2 -AR then apparently induces ERK activation by releasing G␤␥ dimers from the pertussis toxin (PTX)-sensitive G i proteins, followed by activation of the cytosolic tyrosine kinase c-Src, the GTPase Ras, and the MAP kinase kinase kinase, Raf-1. Meanwhile, it has been reported that the switching of ␤ 2 -AR from G s to G i proteins is controlled by ␤-arrestin, which recruits the cAMP-degrading phosphodiesterase 4 to the plasma membrane and thereby alters the activity state of PKA (9). In contrast, Schmitt and Stork (10) report that ERK activation by the ␤ 2 -AR in HEK-293 cells, although also PKA-and c-Src-dependent, is PTX-insensitive and thus apparently does not require ␤ 2 -AR switching to G i proteins, a finding recently confirmed by others using a PKAinsensitive ␤ 2 -AR mutant (11). Furthermore, Schmitt and Stork (10) show that ERK activation by ␤ 2 -AR is not mediated by Ras but by the related GTPase Rap1, activating the MAP kinase kinase kinase B-Raf, but not Raf-1. Interestingly, activation of the ␤ 2 -AR also resulted in Ras activation, but this receptor action was apparently independent of cAMP and PKA (10).

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“…Activation of G i -coupled receptors has been shown to affect phospholipase C and/or PKC activity, either directly or via inhibition of the AC/cAMP transduction pathway in neuronal and nonneuronal cells. [23][24][25] In summary, our findings suggest that the interaction between ERSNA and ARNA is impaired in SHR due to increased activation of ␣ 2 -ARs and AT1 receptors in renal pelvic tissue. The studies in the isolated renal pelvic wall preparation, together with our immunohistochemical studies, 22 suggest that the suppressed ERSNA-ARNA interaction involves postsynaptic ␣ 2 -AR, located on or close to the renal sensory nerves.…”

Section: Mechanisms Involved In the Reduced Responsiveness Of Renal Smentioning

confidence: 96%

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors

2011

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Abstract-Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. The renorenal reflex responses to various stimuli are impaired in spontaneously hypertensive rats (SHR). Because renal tissue density of ␣ 2 -adrenoceptors (ARs) is increased in SHR, we examined whether the ERSNA-induced increases in ARNA are impaired in SHR and, if so, the role of ␣ 2 -ARs. The ARNA responses to increases in ERSNA were impaired in SHR, 2390Ϯ460%⅐seconds, versus in Wistar-Kyoto rats, 6620Ϯ1690%⅐seconds. Renal pelvic release of substance P was not altered by 6250 pmol/L norepinephrine (NE) in SHR but was increased by 250 pmol/L NE in Wistar-Kyoto rats, from 5.7Ϯ0.7 to 12.5Ϯ1.3 pg/min. Renal pelvic administration of the ␣ 2 -AR antagonist rauwolscine enhanced the ERSNA-induced increases in ARNA, 4170Ϯ900%⅐seconds, in SHR but not in Wistar-Kyoto rats. In the presence of rauwolscine, 250 pmol/L NE increased substance P release, from 5.2Ϯ0.3 to 11.2Ϯ0.8 pg/min, in pelvises from SHR. Because angiotensin II suppresses the activation of renal mechanosensory nerves in SHR, we examined whether losartan improved the ERSNA-induced ARNA responses. Losartan had no effect on the ARNA responses or the NE-induced increases in substance P in SHR. However, losartanϩrauwolscine resulted in further enhancement of the responsiveness of the renal sensory nerves to increases in ERSNA and NE in SHR but not in WKY. We conclude that increased activation of renal ␣ 2 -ARs and angiotensin II type 1 receptors contributes to the impaired interaction between ERSNA and ARNA in SHR. Key Words: kidney Ⅲ sensory nerves Ⅲ sympathetic nerves Ⅲ substance P Ⅲ PGE 2 Ⅲ angiotensin T he kidney has a rich supply of sympathetic nerves that innervate all parts of the nephron and the renal vasculature. 1 The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. 2,3 Sympathetic efferent nerve fibers and afferent sensory nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, 2 providing anatomic support for a functional interaction between efferent renal sympathetic nerve activity (ERSNA) and afferent renal nerve activity (ARNA). In normotensive rats, activation of the renal sensory nerves leads to decreases in ERSNA and natriuresis, an inhibitory renorenal reflex response. 1 Not only do increases in ARNA decrease ERSNA but also reflex increases in ERSNA increase ARNA. 2,3 The increased ARNA will, in turn, decrease ERSNA via activation of the renorenal reflexes, a negative-feedback mechanism, to maintain low-level ERSNA.Changes in ERSNA modulate ARNA by the release of norepinephrine (NE), which activates ␣ 1 -adrenoceptors (ARs) and ␣ 2 -ARs on renal sensory nerves, leading to increases and decreases in ARNA, respectively. 2 The physiologic importance of the ERSNA-induced increases in ARNA is underlined by the interactio...

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Inhibition of phospholipase C-ε by Gi-coupled receptors

Cited by 17 publications

References 24 publications

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Epac- and Ca2+-controlled Activation of Ras and Extracellular Signal-regulated Kinases by Gs-coupled Receptors

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors

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Inhibition of phospholipase C-ε by Gi-coupled receptors

Cited by 17 publications

References 24 publications

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves

Epac- and Ca2+-controlled Activation of Ras and Extracellular Signal-regulated Kinases by Gs-coupled Receptors

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α 2 -Adrenoceptors

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Product

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Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors