NPY Regulates Catecholamine Secretion from Human Adrenal Chromaffin Cells

Abstract

The aim of the present work was to find out whether NPY synthesized in human adrenal chromaffin cells controls in an autocrine/paracrine fashion the release of catecholamines by these cells. Accordingly, the constitutive and regulated release of both NPY and catecholamines was measured simultaneously in cultured human chromaffin cells. In addition, by using both RT-PCR and a combination of specific agonists and antagonists, we characterized the expression of NPY receptors on these cells as well as their pharmacology. Our results were as follows. 1) Human chromaffin cells constitutively secrete NPY. 2) Nicotine elicits a rapid increase in the release of both catecholamines and NPY; this release of NPY is more sustained than that of catecholamines. 3) RT-PCR shows expression of Y1, Y2, Y4, and Y5 receptor mRNA by chromaffin cells; these receptors are functional, as various receptor specific agonists elicit an increase in intracellular calcium. 4) Peptide YY, in contrast to NPY, is not able to stimulate the release of catecholamines. This finding was corroborated by the observation that no receptor-specific antagonists were able to reduce constitutive catecholamine release, whereas an NPY-immunoneutralizing antibody markedly attenuated the secretion. Taken together, these data suggest that NPY originating from the adrenal medulla locally enhances the secretion of catecholamines, presumably by acting via the putative y3 receptor.

Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors

“…To date, no single NPY receptor has been cloned with the pharmacology of the Y3 receptor. However, despite its debatable presence, several tissues with Y3 receptor activity have been identified, including but not limited to human adrenal chromaffin cells (36), nucleus tractus salitarii (NTS) (37), cardiac ventricular membrane (38), and rat aortic endothelial cells (39). In adrenal chromaffin cells, the sum of the individual effects of Y1, Y2, Y4, and Y5 receptors has been suggested as the Y3 receptor effect (15).…”

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

“…Primary cell culture of human chromaffin cells Human adrenal glands were obtained from kidney transplant donors and primary cell cultures of human chromaffin cells were performed as previously described (Cavadas et al 2001). Briefly, after enzymatic digestion, the cells were plated on 48 multi-well plates (120 000 chromaffin cells/well) and maintained during 3-5 days in the culture medium: Dulbecco's modified Eagle's medium (DMEM)/Ham's F12, (Invitrogen, Eugene, OR, USA), 10% Fetal Calf Serum (Biochrom, Berlin, Germany), 100 UI/mL penicillin (Sigma Chemical Co.), and 100 lg/mL streptomycin (Sigma Chemical Co.).…”

“…The secretion of catecholamine from chromaffin cells may involve different intracellular pathways such as protein kinase C (PKC), protein kinase A (PKA), and mitogenactivated protein kinase (MAPK) (Morita et al 1987;Cox and Parsons 1997;Cavadas et al 2001;Machado et al 2001). On other hand, as neuronal nitric oxide synthase in the neuronal fibers are in close contact with the adrenal medulla (Bredt et al 1990), some studies suggest that nitric oxide (NO) may act within adrenal chromaffin cells as both an intracellular and intercellular messenger in non-human chromaffin cells (Oset-Gasque et al 1998;Schwarz et al 1998;Vicente et al 2002;Rosmaninho-Salgado et al 2007b).…”

“…We have previously demonstrated that neuropeptide Y (NPY) is synthesized and co-released with catecholamine, and NPY through the activation of NPY Y 3 or Y 1 receptors, stimulates catecholamine release from human and mouse chromaffin cells, respectively (Cavadas et al 2001(Cavadas et al , 2006. The intracellular mechanisms coupled to NPY Y 3 receptor that evokes catecholamine release from human chromaffin cells are not known.…”

NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as a Potential Drug Target

“…NPY is also found in non-adrenergic neurons, in which it is co-localized with -aminobutyric acid (GABA), somatostatin in agouti-related protein (AGRP) containing neurons, acetylcholine, VIP and peptide histidine isoleucine (PHI) [21]. The adrenal medulla is the primary source of circulating NPY known [22,23] though it is also expressed in other peripheral regions, e.g. liver, heart, spleen, bone marrow, adipocytes and peripheral blood cells [24][25][26].…”