Natriuretic Peptide Receptor-B (Guanylyl Cyclase-B) Mediates C-type Natriuretic Peptide Relaxation of Precontracted Rat Aorta

Drewett, J. G.; Fendly, Brian M.; Garbers, David L.; Lowe, David

doi:10.1074/jbc.270.9.4668

Cited by 100 publications

(39 citation statements)

References 41 publications

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“…CNP also can relax vascular preparations from pig, dog, human, and rat (27, 36 -39). In the in vitro models the vasorelaxant effect of CNP is observed at higher concentrations than required for the same effect with ANP (27,36,38) and at a potency consistent with activation of GC-A (2, 7, 27, 36, 38). Plasma levels of endogenous ANP and BNP rise during CNP infusion even at very low infusion rates (24).…”

Section: Resultsmentioning

confidence: 99%

The Guanylyl Cyclase-deficient Mouse Defines Differential Pathways of Natriuretic Peptide Signaling

Lopez¹,

Garbers²,

Kühn³

1997

Journal of Biological Chemistry

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A genetic model of salt-resistant hypertension has been developed recently through disruption of the guanylyl cyclase-A (GC-A) natriuretic peptide receptor gene (Lopez, M. J., Wong, S. K., Kishimoto, I., Dubois, S., Mach, V., Friesen, J., Garbers, D. L., and Beuve, A. (1995) Nature 378, 65-68). These genetically altered mice were used to determine which of the natural peptides with natriuretic peptide-like structures regulate blood pressure through the GC-A receptor. Atrial natriuretic peptide (ANP) or B-type natriuretic peptide (BNP) half-maximally relaxed precontracted aortic rings in wild-type mice at about 24 nM, but failed to relax such aortas in GC-A null mice, even at micromolar concentrations. Ctype natriuretic peptide (CNP), in contrast, caused halfmaximal relaxation at concentrations of 335 and 146 nM in aortas from either wild-type or null mice, respectively, suggesting that this peptide acted through a receptor other than GC-A. Since the in vitro results with aortic smooth muscle do not necessarily reflect the physiology of the smaller blood vessels important in blood pressure regulation, the blood pressures of conscious mice infused with the various peptides were determined. ANP caused decreases in blood pressure when infused at rates of 500 ng/kg/min, a rate which resulted in a plasma concentration of 0.8 nM. In the null mice, in contrast, ANP failed to lower blood pressure even at infusion rates of 50 g/kg/min. Much higher infusion rates for CNP (50 g/kg/min), which yielded final plasma concentrations of 18.3 nM, were required to lower blood pressure in wild-type mice, but the effects of CNP were not altered in GC-A null mice. Thus, two natriuretic peptides (ANP, BNP) act through GC-A whereas another (CNP) acts through another receptor to regulate blood pressure.

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Section: Resultsmentioning

confidence: 99%

The Guanylyl Cyclase-deficient Mouse Defines Differential Pathways of Natriuretic Peptide Signaling

Lopez¹,

Garbers²,

Kühn³

1997

Journal of Biological Chemistry

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“…Therefore, we chose rat vascular smooth A10 cells because vascular smooth muscle is a known target for natriuretic peptides (13,49). However, because of discrepancies in the literature regarding whether A10 cells express NPR-A (34,41,50) or NPR-B (51-53), we first determined the expression profile of natriuretic peptide receptors in these cells.…”

Section: Resultsmentioning

confidence: 99%

Vasopressin-dependent Inhibition of the C-type Natriuretic Peptide Receptor, NPR-B/GC-B, Requires Elevated Intracellular Calcium Concentrations

Abbey¹,

Potter

2002

Journal of Biological Chemistry

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Natriuretic peptides bind their cognate cell surface guanylyl cyclase receptors and elevate intracellular cGMP concentrations. In vascular smooth muscle cells, this results in the activation of the type I cGMP-dependent protein kinase and vasorelaxation. In contrast, pressor hormones like arginine-vasopressin, angiotensin II, and endothelin bind serpentine receptors that interact with G q and activate phospholipase C␤. The products of this enzyme, diacylglycerol and inositol trisphosphate, activate the conventional and novel forms of protein kinase C (PKC) and elevate intracellular calcium concentrations, respectively. The latter response results in vasoconstriction, which opposes the actions of natriuretic peptides. Previous reports have shown that pressor hormones inhibit natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell types. Although the mechanism for this inhibition remains unknown, it has been universally accepted that PKC is an obligatory component of this pathway primarily because pharmacologic activators of PKC mimic the inhibitory effects of these hormones. Here, we show that in A10 vascular smooth muscle cells, neither chronic PKC down-regulation nor specific PKC inhibitors block the AVP-dependent desensitization of NPR-B even though both processes block PKC-dependent desensitization. In contrast, the cell-permeable calcium chelator, BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N,Ntetraacetic acid, tetraacetoxymethyl ester), abrogates the AVP-dependent desensitization of NPR-B, and ionomycin, a calcium ionophore, mimics the AVP effect. These data show that the inositol trisphosphate/calcium arm of the phospholipase C pathway mediates the desensitization of a natriuretic peptide receptor in A10 cells. In addition, we report that CNP attenuates AVPdependent elevations in intracellular calcium concentrations. Together, these data reveal a dominant role for intracellular calcium in the reciprocal regulation of these two important vasoactive signaling systems.

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“…The GC A receptor, also known as natriuretic peptide receptor-A, is the physiological receptor for ANP, and possibly also for brain natriuretic peptide, whereas the GC B receptor probably mediates the effects of C-type natriuretic peptide. 30,31 The stimulation of the GC receptors is associated with a marked increase in intracellular cGMP, the second messenger of natriuretic peptides. Clearance receptors bind with high affinity to all natriuretic peptides, but do not generate cGMP on ligand binding, and appear to play an important role in the clearance of natriuretic peptides from the circulation.…”

Section: Discussionmentioning

confidence: 99%

Atrial natriuretic peptide antagonizes endothelin-induced calcium increase and cell contraction in cultured human hepatic stellate cells

et al. 1999

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Several lines of evidence indicate that hepatic stellate cells (HSCs), besides their crucial role in the increased synthesis of extracellular matrix components that occurs in chronic liver diseases, may participate in the regulation of sinusoidal blood flow. [1][2][3] Morphological studies have shown that HSCs have numerous cell processes that surround the sinusoids and contain cytosolic proteins characteristic of contractile cells. [4][5][6][7][8][9][10] Moreover, HSCs have receptors for a large number of vasoconstrictor substances, including endothelin-1, arginine vasopressin, thrombin, thromboxanes, and angiotensin II. 6,8,[11][12][13][14][15] Finally, the stimulation of HSCs in culture with these vasoconstrictor substances is associated with a marked increase in intracellular calcium concentration ([Ca 2ϩ ] i ) and cell contraction, 6,[8][9][10][11][12][13][14][15] suggesting that the contractile function of HSCs may be regulated by the action of vasoconstrictors.In contractile cells, the effects of vasoconstrictor agonists may be attenuated by the action of vasodilators. In fact, the state of contraction/relaxation of contractile cells is dependent on the interaction between vasoconstrictor and vasodilator factors. 16 In clear contrast with the large amount of information available on the effects of vasoconstrictor factors on HSCs, little is known about the effects of vasodilating substances on these cells. It has been shown that prostaglandins and nitric oxide produce relaxation of HSCs in culture and reduce the effects of vasoconstrictor agents, which suggests that these vasodilator factors may act as paracrine or autocrine regulators of HSCs' contractility. 10,12 However, it is not known whether the contractile function of HSCs may also be regulated by circulating vasodilator substances. One of the most important circulating vasodilators is atrial natriuretic peptide (ANP), a peptide synthesized in atrial myocytes, which besides its potent natriuretic action has important effects in the circulation by antagonizing the effects of vasoconstrictors. 17,18 Therefore, the aims of the current study were to determine (1) whether human HSCs have receptors for ANP, and (2) whether the stimulation of human HSCs with ANP in vitro reduces the effects elicited by contractile agonists on these cells. MATERIALS AND METHODSIsolation and Culture of Human and Rat Hepatic Stellate Cells. Human HSCs were isolated from fragments of normal human livers obtained from resections of liver metastases as described in detail elsewhere. 15,19 Briefly, after a combined digestion of liver tissue with

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Natriuretic Peptide Receptor-B (Guanylyl Cyclase-B) Mediates C-type Natriuretic Peptide Relaxation of Precontracted Rat Aorta

Cited by 100 publications

References 41 publications

The Guanylyl Cyclase-deficient Mouse Defines Differential Pathways of Natriuretic Peptide Signaling

The Guanylyl Cyclase-deficient Mouse Defines Differential Pathways of Natriuretic Peptide Signaling

Vasopressin-dependent Inhibition of the C-type Natriuretic Peptide Receptor, NPR-B/GC-B, Requires Elevated Intracellular Calcium Concentrations

Atrial natriuretic peptide antagonizes endothelin-induced calcium increase and cell contraction in cultured human hepatic stellate cells

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