Cellular and Molecular Aspects of the A-Type Natriuretic Peptide

Gardner, David G.; Wu, Jianming; Kovac̆ic̆-Milivojević, Branka

doi:10.1007/978-1-4612-3960-4_5

Cited by 5 publications

(2 citation statements)

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“…NPR-A mediates many of the effects of ANF and BNP, circulating hormones released by myocardial cells in response to hormonal, metabolic, and mechanical stimuli that have potent natriuretic, diuretic, and vasorelaxant activities (Gardner et al 1997). In contrast, NPR-B may be particularly important in the autocrine or paracrine control of cGMP production, as its principal ligand, CNP, does not circulate at high levels (Igaki et al 1996), and is often produced by cells juxtaposed to cell types bearing the NPR-B receptor.…”

Section: Introductionmentioning

confidence: 99%

cAMP inhibits natriuretic peptide receptor-B activity and increases C-type natriuretic peptide in FRTL-5 rat thyroid cells

Sellitti

Puggina²,

Lagranha³

et al. 2004

Journal of Endocrinology

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C-type natriuretic peptide (CNP) and its cognate guanylyl cyclase receptor, the natriuretic peptide receptor B (NPR-B) together constitute a regulatory system that controls cell function via the generation of intracellular cyclic GMP. In this report we have examined the role of cAMP signaling in the regulation of CNP and NPR-B activity in the FRTL-5 rat thyroid follicular cell line. As had been observed earlier with TSH, the cAMP mimetic, dibutyryl cAMP (dbcAMP; 1 mM) induced a significant reduction in CNP-stimulated cGMP generation that was first apparent after 6 h of treatment. The inhibitory effect of dbcAMP on NPR-B was dose dependent, with an EC 50 of 0·2 mM.Pretreatment of FRTL-5 cells with either of two protein kinase A (PKA) inhibitors, KT-5720 and H-89, failed to curtail the dbcAMP reduction in NPR-B activity, suggesting that the cAMP pathway leading to inhibition of NPR-B is PKA independent. Whereas either a 30-min or a 24-h treatment with the protein kinase C-activator phorbol myristate acetate failed to alter maximal levels of CNP-stimulated cGMP, a 24-h exposure to the calcium ionophore A23187 reduced CNP-stimulated cGMP to about one-third of control. Pretreatment of FRTL-5 cells with the cell-permeable calcium chelator 1,2 bis(2-aminophenoxy)ethane-N,N,N 1 ,N 1 -tetraacetic acid, tetraacetoxymethyl ester completely abrogated the cAMP-induced reduction of CNP-stimulated cGMP. Real-time PCR showed no effect of dbcAMP on NPR-B transcript at 3 and 6 h, but indicated a 40% reduction in transcript by dbcAMP at 24 h. In contrast, real-time PCR indicated a 5-fold increase in CNP transcript at 3 h, reaching 15·4-fold above control at 6 h in cells treated with dbcAMP. In addition, immunofluorescence staining of FRTL-5 cells with a specific antibody for CNP-22 showed the presence of cytoplasmic CNP that was upregulated by incubation with either TSH or dbcAMP.These results suggested that cAMP signaling regulates the natriuretic peptide system in rat thyroid cells by increasing CNP expression, and reducing NPR-B activity. This latter action of cAMP appears to be both PKA independent and calcium dependent, and provides support for a dominant role for calcium in the regulation of NPR-B in the rat thyroid.

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Section: Introductionmentioning

confidence: 99%

cAMP inhibits natriuretic peptide receptor-B activity and increases C-type natriuretic peptide in FRTL-5 rat thyroid cells

Sellitti

Puggina²,

Lagranha³

et al. 2004

Journal of Endocrinology

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show abstract

“…Although, the main sources of ANP are the atria, there is a possibility that ANP may be excreted from the ventricles physiologically (e.g., in late fetal and early neonatal periods) or pathophysiologically (e.g., following hemodynamic overload) in patients with cardiac hypertrophy, heart failure, and atrial fibrillations 3,4 . Expression of the ANP gene has also been documented in a number of extra‐atrial tissues including the central nervous system, aortic arch, kidney, gonadotropes of the anterior pituitary gland, thymus, lung, and macrophage 4 . Globits et al 5 found strong relation between ANP levels and both left and right atrial volumes.…”

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confidence: 99%