Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin‐1β: role of neuropeptide Y and nitric oxide

Rosmaninho‐Salgado, Joana; Araújo, Inês M.; Álvaro, Ana Rita; Mendes, Alexandrina Ferreira; Ferreira, Lígia; Grouzmann, Eric; Mota, A.; Duarte, Emília P.

doi:10.1111/j.1471-4159.2009.06023.x

Cited by 31 publications

(35 citation statements)

References 74 publications

(192 reference statements)

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“…In turn, neuropeptides are known to regulate the synthesis and release of cosecreted catecholamines. For example, it has been reported that vasoactive intestinal peptide, secretin, and neuropeptide Y increase catecholamine synthesis by activation of tyrosine hydroxylase in human adrenal chromaffin cells (Ip et al, 1984;Cavadas et al, 2001;Rosmaninho-Salgado et al, 2009). The regulatory circuit is completed when this neuropeptide-triggered increase in catecholamines eventually leads to a reduction in neuropeptide production, accomplished by catecholaminergic inhibition of neuropeptide processing enzymes, as demonstrated in the present study.…”

supporting

confidence: 73%

Regulation of Neuropeptide Processing Enzymes by Catecholamines in Endocrine Cells

Helwig¹,

Vivoli²,

Fricker³

et al. 2011

Mol Pharmacol

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Treatment of cultured bovine adrenal chromaffin cells with the catecholamine transport blocker reserpine was shown previously to increase enkephalin levels severalfold. To explore the biochemical mechanism of this effect, we examined the effect of reserpine treatment on the activities of three different peptide precursor processing enzymes: carboxypeptidase E (CPE) and the prohormone convertases (PCs) PC1/3 and PC2. Reserpine treatment increased both CPE and PC activity in extracts of cultured chromaffin cells; total protein levels were unaltered for any enzyme. Further analysis showed that the increase in CPE activity was due to an elevated V max , with no change in the K m for substrate hydrolysis or the levels of CPE mRNA. Reserpine activation of endogenous processing enzymes was also observed in extracts prepared from PC12 cells stably expressing PC1/3 or PC2. In vitro experiments using purified enzymes showed that catecholamines inhibited CPE, PC1/3, and PC2, with dopamine quinone the most potent inhibitor (IC 50 values of ϳ50 -500 M); dopamine, norepinephrine, and epinephrine exhibited inhibition in the micromolar range. The inhibition of purified CPE with catecholamines was time-dependent and, for dopamine quinone, dilution-independent, suggesting covalent modification of the protein by the catecholamine. Because the catecholamine concentrations found to be inhibitory to PC1/3, PC2, and CPE are well within the physiological range found in chromaffin granules, we conclude that catecholaminergic transmitter systems have the potential to exert considerable dynamic influence over peptidergic transmitter synthesis by altering the activity of peptide processing enzymes.

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supporting

confidence: 73%

Regulation of Neuropeptide Processing Enzymes by Catecholamines in Endocrine Cells

Helwig¹,

Vivoli²,

Fricker³

et al. 2011

Mol Pharmacol

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“…The inclusion of the NPY Y1 receptor antagonist (BIBP 3226) or immunoneutralization of NPY suppressed the IL-1b stimulated catecholamine release. This investigation has recently been extended to demonstrate a similar IL-1b-induced catecholamine secretion from isolated human adrenal medullary chromaffin cells (Rosmaninho-Salgado et al 2009). As with the mouse studies, IL-1b also increased NPY secretion and blockade of the NPY receptor (or the inclusion of anti-NPY antibodies) suppressed the elevation in catecholamine secretion.…”

Section: Interleukin-1mentioning

confidence: 85%

“…The IL-1b-stimulated catecholamine secretion was accompanied by an increase in ser-40 phosphorylation of tyrosine hydroxylase and a delayed rise in the enzyme's expression-responses indicative of increased catecholamine synthesis. The inclusion of selected pharmacological inhibitors revealed a complex signalling pathway but led Rosmaninho-Salgado et al (2009) to suggest that IL-1b stimulation of catecholamine release from chromaffin cells involves three different pathways namely, ERK1/2, NO-PKC and NO-guanylyl cyclase (Rosmaninho-Salgado et al 2009). While further experiments will be required to tease apart these complexities, these data indicate that IL-1b and NPY are involved in a regulatory loop between immune and adrenal medullary cells which is likely to be of relevance during inflammatory conditions.…”

Section: Interleukin-1mentioning

confidence: 99%

Cytokine Interactions with Adrenal Medullary Chromaffin Cells

et al. 2010

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It is generally accepted that a bi-directional or reciprocal interaction occurs between the immune and neuroendocrine systems, and that this relationship is important for the appropriate physiological functioning of both systems. Similarly, an imbalance in this relationship may contribute to a number of pathologies, most notably those relating to stress. The aim of this article is to consider the interaction of cytokines with the adrenal medulla, a potentially important player in this relationship. The chromaffin cells of the adrenal medulla release catecholamines and a range of biologically active peptides in response to a wide variety of stress-related signals. A growing body of evidence indicates that this stress response is influenced by, and in turn has influence upon, immune signalling. This brief review will focus primarily on the best-described adrenal medullary active cytokines, namely interferon-α, interleukin-6, interleukin-1α/β and tumour necrosis factor-α. In each case, three key issues will be addressed: the physiologically relevant source of the cytokine; the intracellular signalling events arising from activation of its receptor and finally the cellular consequences of such activation in terms of modulation of gene expression and the secretory output of the chromaffin cells.

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“…In human chromaffin cells, NPY has been shown to positively regulate catecholamine secretion (Rosmaninho-Salgado et al 2009). Among the six genes, Y1, Y2, Y3, Y4, Y5, and Y6 that have been described as coding for NPY receptors, Y6 is a pseudogene in human that codes for a truncated nonfunctional protein.…”

Section: Introductionmentioning

confidence: 99%

Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Thouënnon¹,

Aimar²,

Tanguy³

et al. 2010

Endocrine-Related Cancer

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Pheochromocytomas are catecholamine-producing tumors which are generally benign, but which can also present as or develop into malignancy. Molecular pathways of malignant transformation remain poorly understood. Pheochromocytomas express various trophic peptides which may influence tumoral cell behavior. Here, we investigated the expression of trophic amidated peptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY), and adrenomedullin (AM), and their receptors in benign and malignant pheochromocytomas in order to assess their potential role in chromaffin cell tumorigenesis and malignant transformation. PACAP, NPY, and AM are expressed in the majority of pheochromocytomas studied; NPY exhibiting the highest mRNA levels relative to reference genes. Although median gene expression or peptide levels were systematically lower in malignant compared to benign tumors, no statistically significant difference was found. Among all the receptors of these peptides that were analyzed, only the AM receptor RDC1 displayed a differential expression between benign and malignant pheochromocytomas. This receptor exhibited a fourfold higher expression in malignant than in benign tumors. AM and stromal cell-derived factor 1, which has also been described as a ligand for RDC1, increased the number of human pheochromocytoma cells in primary culture and exerted anti-apoptotic activity on rat pheochromocytoma PC12 cells. In addition, RDC1 gene silencing decreased the number of viable PC12 cells. This study shows the expression of several trophic peptides and their receptors in benign and malignant pheochromocytomas, and suggests that AM and its RDC1 receptor could be involved in chromaffin cell tumorigenesis through pro-survival effects. Therefore, AM and RDC1 may represent valuable targets for the treatment of malignant pheochromocytomas.

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Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin‐1β: role of neuropeptide Y and nitric oxide

Cited by 31 publications

References 74 publications

Regulation of Neuropeptide Processing Enzymes by Catecholamines in Endocrine Cells

Regulation of Neuropeptide Processing Enzymes by Catecholamines in Endocrine Cells

Cytokine Interactions with Adrenal Medullary Chromaffin Cells

Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

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