Activation of the Particulate and Not the Soluble Guanylate Cyclase Leads to the Inhibition of Ca2+ Extrusion through Localized Elevation of cGMP

Zolle, Olga; Lawrie, Alison M.; Simpson, Alec W.M.

doi:10.1074/jbc.m000786200

Cited by 55 publications

(48 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the downstream actions of GMP (37) occur through its binding and subsequent activation of PKG, but cGMP also directly regulates ion channels (38 -41) and phosphodiesterases (42). There is recent evidence that particulate, but not soluble, cyclases have potent effects on plasma membrane control of calcium homeostasis (25). Indeed, whereas it is generally believed that such spatially and temporally distinct cGMP signals can coexist within cells, a precise mechanism for differentiating NP-versus NO-specified cellular events has never been proposed.…”

Section: Resultsmentioning

confidence: 99%

“…Downstream NP effects that have been directly tied to activated PKG include modulation of the L-type calcium channel (21,22) and cross-talk with heterologous receptors, such as G protein-coupled receptors (23,24). Furthermore, there is recent evidence that the membrane-bound guanylyl cyclase, NPRA, but not soluble cyclases that are activated by nitric oxide, has potent effects on plasma membrane control of the calcium ATPase pump (25), suggesting that NO-and NP-mediated effects are compartmentalized in cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Atrial Natriuretic Peptide Induces Natriuretic Peptide Receptor-cGMP-dependent Protein Kinase Interaction

Airhart

Yang

Roberts

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Circulating natriuretic peptides such as atrial natriuretic peptide (ANP) counterbalance the effects of hypertension and inhibit cardiac hypertrophy by activating cGMP-dependent protein kinase (PKG). Natriuretic peptide binding to type I receptors (NPRA and NPRB) activates their intrinsic guanylyl cyclase activity, resulting in a rapid increase in cytosolic cGMP that subsequently activates PKG. Phosphorylation of the receptor by an unknown serine/threonine kinase is required before ligand binding can activate the cyclase. While searching for downstream PKG partners using a yeast two-hybrid screen of a human heart cDNA library, we unexpectedly found an upstream association with NPRA. PKG is a serine/threonine kinase capable of phosphorylating NPRA in vitro; however, regulation of NPRA by PKG has not been previously reported. Here we show that PKG is recruited to the plasma membrane following ANP treatment, an effect that can be blocked by pharmacological inhibition of PKG activation. Furthermore, PKG participates in a ligand-dependent gainof-function loop that significantly increases the intrinsic cyclase activity of the receptor. PKG translocation is ANP-dependent but not nitric oxide-dependent. Our results suggest that anchoring of PKG to NPRA is a key event after ligand binding that determines distal effects. As such, the NPRA-PKG association may represent a novel mechanism for compartmentation of cGMP-mediated signaling and regulation of receptor sensitivity.The natriuretic peptides (NPs) 1 are produced by the heart, the vasculature, and the kidney and are an ancient family of polypeptide hormones that regulate mammalian blood volume and blood pressure. More recently, the ability of NPs to modulate cell proliferation (1) and cardiac hypertrophy (2) has been demonstrated. Physiologically important NP actions include natriuresis (3), vasodilation (4), and ubiquitous inhibitory actions such as inhibition of smooth muscle proliferation (1, 5), cardiac fibroblast proliferation (6), cardiomyocyte hypertrophy (2, 7-9), sympathetic tone (10), renin-angiotensin-aldosterone activation (11), and hypothalamic-pituitary-adrenal axis signaling (12)(13)(14). In disease states such as heart failure, NP actions may be limited by resistance to hormone effects (15)(16)(17) that are at least in part because of insensitivity of the receptor itself (18).Natriuretic peptide binding to type I receptors (NPRA and NPRB) on target cells activates their intrinsic guanylyl cyclase activity, resulting in a rapid increase in cGMP. Diffusible cGMP acts as a second messenger primarily by stimulating PKG (19). PKG is the major mediator of cGMP-induced smooth muscle relaxation (20). Downstream NP effects that have been directly tied to activated PKG include modulation of the L-type calcium channel (21, 22) and cross-talk with heterologous receptors, such as G protein-coupled receptors (23, 24). Furthermore, there is recent evidence that the membrane-bound guanylyl cyclase, NPRA, but not soluble cyclases that are activated by nitric oxide, ha...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Atrial Natriuretic Peptide Induces Natriuretic Peptide Receptor-cGMP-dependent Protein Kinase Interaction

Airhart

Yang

Roberts

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…For instance, it has been shown that GC-A, but not soluble GC, has potent effects on plasma membrane control of the calcium ATPase pump. 122 Interestingly, a very recent study has demonstrated that ANP/GC-A, but not NO/soluble GC, stimulates the translocation of PKG I to the plasma membrane. 92 Hence, the mechanisms for compartmentation of cGMP-mediated signaling within different cell types remain an intriguing issue.…”

Section: Future Directionsmentioning

confidence: 99%

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Kühn

2003

Circulation Research

241

161

View full text Add to dashboard Cite

Abstract-Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases. (Circ Res. 2003;93:700-709.)

show abstract

“…Furthermore, the intracellular cGMP concentrations differ in different cell types relevant to vascular relaxation and cardiac function 23, 24. Natriuretic peptides activate different downstream signaling pathways, resulting in decreased intracellular calcium by regulating the activity of L‐type calcium channels and phospholamban, compared with NO, which decreases calcium sensitivity of myofilaments 23, 25, 26, 27. Thus, cGMP originating from natriuretic peptides and NO play distinct roles in the control of vascular relaxation, which is further modulated by the differential activity of PDE‐5 inhibitors in different vascular beds 28, 29.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Pharmacokinetic and Pharmacodynamic Drug–Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild‐to‐Moderate Hypertension

Hsiao¹,

Langenickel

Petruck³

et al. 2017

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open‐label, three‐period, single sequence study, patients with mild‐to‐moderate hypertension (153.8 ± 8.2 mmHg mean systolic blood pressure (SBP)) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil coadministration. When coadministered with sildenafil, the AUC and Cmax of valsartan decreased by 29% and 39%, respectively. Coadministration of sacubitril/valsartan and sildenafil resulted in a greater decrease in BP (–5/–4/–4 mmHg mean ambulatory SBP/DBP/MAP (mean arterial pressure)) than with sacubitril/valsartan alone. Both treatments were generally safe and well tolerated in this study; however, the additional BP reduction suggests that sildenafil should be administered cautiously in patients receiving sacubitril/valsartan. Unique identifier: NCT01601470.

show abstract

Activation of the Particulate and Not the Soluble Guanylate Cyclase Leads to the Inhibition of Ca2+ Extrusion through Localized Elevation of cGMP

Cited by 55 publications

References 46 publications

Atrial Natriuretic Peptide Induces Natriuretic Peptide Receptor-cGMP-dependent Protein Kinase Interaction

Atrial Natriuretic Peptide Induces Natriuretic Peptide Receptor-cGMP-dependent Protein Kinase Interaction

Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A

Evaluation of Pharmacokinetic and Pharmacodynamic Drug–Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild‐to‐Moderate Hypertension

Contact Info

Product

Resources

About