Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation

White, Richard E.; Lee, A. B.; Shcherbatko, Anatoly; Lincoln, Thomas M.; Schönbrunn, Agnes; Armstrong, David M.

doi:10.1038/361263a0

Cited by 247 publications

(144 citation statements)

References 28 publications

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“…Furthermore, erythrocytes have guanylate-cyclase activity stimulated by these ANP fragments like other cells with well-established ANP-specific receptors (Brenner et al, 1990;Leitman et al, 1986Leitman et al, ,1988O'Donnell et al, 1986O'Donnell et al, ,1987Owen et al, 1987;Smith and Lincoln, 1987;White et al, 1993). We suggest therefore that human erythrocytes can be target cells for ANP fragments possessing at least Phe-Arg and Ser-Ser at the carboxy and amino termini, respectively, in the blood stream.…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of Ser-Ser at the amino terminus also reduced the potencies of ANP peptides to stimulate vasorelax-ation Owen et al, 1987) and to act on cellular Na+/K+ cotransport O'Grady et al, 1985;Owen et al, 1987). cGMP mediates some of the physiological effects of ANP (Brenner et al, 1990) including alterations of ion-transport systems (Clemo et al, 1992;O'Donnell et al, 1986;White et al, 1993). We have shown that, like other cell types (Leitman et al, 1988;Smith and Lincoln, 1987), the addition of ANP-I11 (10 pM) to erythrocytes produces a rapid but transient increase in cellular cGMP concentration (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange

Petrov

Améry

Lijnen

1994

European Journal of Biochemistry

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Human atrial natriuretic peptide (ANP) fragments ANP-(127-150) or ANP-I11 and ANP-(127-149) or ANP-I1 activate Na+/H+ exchange in human erythrocytes at concentrations as low as 1 pM. Both ANP-(127-147) or ANP-I and ANP-(129-150) or des-Ser5, Ser6-ANP-I11 have no effect on erythrocyte Na+/H+ exchange. ANP-I11 also produces a time-dependent increase of intraerythrocyte guanosine 3',5'-phosphate (cGMP) Concentration. M&B 22,948, a specific inhibitor of cGMP phosphodiesterase, increases Na+/H+ exchange and the intracellular concentration of cGMP. Both 8-bromoguanosine 3',5'-phosphate (8-Br-cGMP) and dibutyryl-cGMP mimic the effect of ANP-I11 on erythrocyte Na+/H+ exchange. Our data suggest that human erythrocytes possess guanylate-cyclase activity stimulated by ANP-I11 and that activation of Na+/H+ exchange by this peptide is mediated by cGMP. Human erythrocytes display a high degree of sensitivity to ANP-I11 or ANP-I1 and a specificity for ANP-fragment structures just as cells with established ANP-specific receptors.Atrial natriuretic peptides (ANP) act on the Na+/H+-exchange rate in cells, which contain specific ANP receptors, through the elevation of intracellular guanosine 3',5'-phosphate (cGMP) concentration (Semrad et al., 1990) or via a cGMP-independent pathway (Gupta et al., 1989). Semrad et al. (1990) have reported a cGMP-mediated inhibition of the Na+/H+-exchange rate by ANP in chicken enterocytes, whereas Gupta et al. (1989) found a cGMP-independent stimulation of the Na+/H+-exchange rate in rabbit aorta segments.Specific receptors for ANP fragments in human erythrocytes have not been determined. There is also controversy whether or not intracellular cGMP synthesis occurs. Indeed, cholinergic agonists stimulate (Tang et al., 1984) or do not affect (Sekar and Hokin, 1986) cGMP production, and guanylate-cyclase activity has not been determined (Bohme et al., 1974) in human erythrocytes. Basal intraerythrocyte cGMP concentration is attributed to its passive uptake (deBari and Bennun, 1982). In the present study we report that human (h)ANP-I11 increases both Na+/H+ exchange and intracellular cGMP concentration in human erythrocytes. Its effect is mimicked by 8-Br-cGMP or dibutyryl-cGMP. The effects of other hANP fragments (ANP-11, ANP-I, des-Ser5, Ser6-ANP-111) on the Na+/H+ exchange depend on their molecular structures.Correspondence to P. Lijnen, Hypertension Unit, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, BelgiumAbbreviations. ANP, atrial natriuretic peptide ; cGMP, guanosine 3',S'-phosphate; iBuMeXan, 3-isobutyl-I-methylxanthine; M&B 22,948, 2-O-propoxyphenyl-8-azapurin-6-one; 8-Br-cGMP, 8-bromo-guanosine 3',5'-phosphate; ANF, atrial natriuretic factor; h, human. MATERIALS AND METHODS Erythrocyte preparationBlood from healthy donors was drawn into heparinized tubes and centrifuged at 2000 g for 7 min at 4°C. The plasma and buffy coat were removed by aspiration, and the erythrocytes were then washed four times with an ice-cold solution consisting of 150 mM KC1,0.15 mM MgC1, and 10 mM glucose. The ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange

Petrov

Améry

Lijnen

1994

European Journal of Biochemistry

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“…One mechanism suggests that PKG activates maxi-K channels through a direct phosphorylation of the channel protein or a regulatory subunit (17, 19 -21); this process can be reversed by phosphatase 2A (22). In contrast, the second mechanism proposes that PKG activates maxi-K channels indirectly via a PKG-dependent activation of protein phosphatase 2A (23,24), which may directly dephosphorylate maxi-K channels. Alternatively, protein phosphatase 2A may exert its effect indirectly.…”

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confidence: 98%

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Alioua¹,

Tanaka²,

Wallner³

et al. 1998

Journal of Biological Chemistry

164

129

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Native large conductance, voltage-dependent, and Ca 2؉ -sensitive K ؉ channels are activated by cGMP-dependent protein kinase. Two possible mechanisms of kinase action have been proposed: 1) direct phosphorylation of the channel and 2) indirect via PKG-dependent activation of a phosphatase. To scrutinize the first possibility, at the molecular level, we used the human poreforming ␣-subunit of the Ca 2؉ -sensitive K ؉ channel, Hslo, and the ␣-isoform of cGMP-dependent protein kinase I. In cell-attached patches of oocytes co-expressing the Hslo channel and the kinase, 8-Br-cGMP significantly increased the macroscopic currents. This increase in current was due to an increase in the channel voltage sensitivity by ϳ20 mV and was reversed by alkaline phosphatase treatment after patch excision. In inside-out patches, however, the effect of purified kinase was negative in 12 of 13 patches. In contrast, and consistent with the intact cell experiments, purified kinase applied to the cytoplasmic side of reconstituted channels increased their open probability. This stimulatory effect was absent when heat-denatured kinase was used. Biochemical experiments show that the purified kinase incorporates ␥-33 P into the immunopurified Hslo band of ϳ125 kDa. Furthermore, in vivo phosphorylation largely attenuates this labeling in back-phosphorylation experiments. These results demonstrate that the ␣-subunit of large conductance Ca 2؉ -sensitive K ؉ channels is substrate for G-I␣ kinase in vivo and support direct phosphorylation as a mechanism for PKG-I␣-induced activation of maxi-K channels.

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“…This may be another general mechanism contributing to the reduction in [Ca2~]~produced by cGMP agonists in many cells. cGMP and PKG stimulate Ca2-activated potassium channels in rat pituitary tumor cells (White et al, 1993). These effects are mimicked by ANP, are preceded by a rapid and potent stimulation of cGMP production, and require PKG activity.…”

Section: Ion Channelsmentioning

confidence: 99%

“…The phosphatase inhibitor okadaic acid blocks the effect of PKG, revealing a requirement for protein dephosphorylation. The PKG substrate mediating this action has been suggested to be phosphatase 2A itself or a regulator of this enzyme (White et al, 1993), a proposal yet to be directly tested. Regulation of Ca2~-activatedKc hannels by PKG has also been shown in neurons.…”

Section: Ion Channelsmentioning

confidence: 99%

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

Wang

Robinson

1997

Journal of Neurochemistry

262

128

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Nitric oxide (NO) and natriuretic peptide hormones play key roles in a surprising number of neuronal functions, including learning and memory. Most data suggest that they exert converging actions by elevation of intracellular cyclic GMP (cGMP) levels through activation of soluble and particulate guanylyl cyclases. However, cGMP is only the starting point for multiple signaling cascades, which are now beginning to be defined. A primary action of elevated cGMP levels is the stimulation of cGMP-dependent protein kinase (PKG), the major intracellular receptor protein for cGMP, which phosphorylates substrate proteins to exert its actions. It has become increasingly clear that PKG mediates some of the neuronal effects of cGMP, but how is not yet clear. One clear illustration of this pathway has been reported in striatonigral nerve terminals, where NO mediates phosphorylation of the protein phosphatase regulator dopamine-and cyclic AM P-regulated phosphoprotein having a molecular mass of 32,000 (DARPP-32) by PKG. There are remarkably few PKG substrates in brain whose identities are known. A survey of these proteins and those known from other tissues that might also be found in the nervous system reveals the key molecular sites where cGMP and PKG signaling is likely to be regulating neural function. These potential substrates are critically placed to have profound effects on the protein phosphorylation network through regulation of protein phosphatases, intracellular calcium levels, and the function of many ion channels and neurotransmitter receptors. The brain also contains a rich diversity of specific PKG substrates whose identities are not yet known. Their future identification will provide exciting new leads that will permit better understanding of the role of PKG signaling in both basic and higher orders of brain function. Key Words: Protein phosphorylation-Cyclic GMP-Cyclic GMP-dependent protein kinase-BrainNeuron-Neurotransmitter release. J. Neurochem. 68, 443-456 (1997).The widespread biological importance of cyclic GMP (cGMP) signaling through cGMP-dependent protein kinase (PKG) has been slow to be appreciated. Despite an exciting flourish of activity in the late I 960s and early 1970s when both cGMP and PKG were discovered, research largely languished for many years and was focused in only a small number of laboratories. This was probably due to the difficulty in determining how this signaling system was activated, what biological processes it regulated, and what substrates of PKG might mediate its actions. PKG' s role in smooth muscle relaxation has been the most significant area of productive research. It was not until more recent years that it was discovered that two pathways lead to cGMP signaling, via natriuretic peptides such as atrial natriuretic peptide (ANP) and soluble gases such as nitric oxide (NO) and carbon monoxide, which elevate intracellular cGMP levels through activation of particulate (GC-P) and soluble (GC-S) guanylyl cyclases (Fig. 1). In the last few years there has been an expl...

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Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation

Cited by 247 publications

References 28 publications

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

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Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation

Cited by 247 publications

References 28 publications

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na+/H+ exchange

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na+/H+ exchange

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

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Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange

Role of cyclic GMP in atrial‐natriuretic‐peptide stimulation of erythrocyte Na⁺/H⁺ exchange