Neuropeptide-Y (NPY) is a 36-amino acid peptide, which belongs, along with peptide YY (PYY), to the pancreatic polypeptide (PP) family. The members of this family of peptides act via G protein-coupled receptors (Rs), six subtypes of which (from Y1- to Y6-R) have been identified. NPY and PYY preferentially bind the Y1-R, Y2-R and Y5-R, while PP mainly acts via the Y4-R. Evidence has been provided that the Y3-R is selective for NPY. NPY and Y-Rs are expressed in the adrenal gland (preferentially adrenal medulla) and pheochromocytomas, where they exert various autocrine-paracrine regulatory functions. Findings indicate that NPY is co-released with catecholamines under a variety of stimuli, including splanchnic nerve and cholinergic- and nicotinic-receptor activation. NPY, mainly acting via the Y1-R, Y2-R and Y3-R, either inhibits catecholamine secretion from bovine adrenal chromaffin cells or stimulates catecholamine secretion from adrenomedullary cells of humans and rats. NPY inhibits aldosterone secretion from dispersed zona glomerulosa (ZG) cells, but this effect has probably to be considered non-specific and toxic in nature, since it is obtained only using micromolar concentrations of the peptide. In contrast, NPY appears to modulate the secretory response of dispersed rat ZG cells to their main agonists (ACTH, angiotensin-II and potassium). However, there is indication that the main effect of NPY on the ZG in rats is indirect and involves the local release of catecholamines, which in turn, acting via β-adrenoceptors, enhance the secretion of aldosterone. The prolonged treatment with NPY is also able to enhance the growth of the rat ZG. In contrast, the effects of NPY on glucocorticoid secretion from zona fasciculata-reticularis cells are negligible and doutbful. The physiological relevance of the effects of NPY on adrenal medulla and ZG remains to be addressed by future experimental studies employing more selective and potent Y-R antagonists. In contrast, indirect evidence is available that endogenous NPY system may play an important role in the modulation of adrenal functions under paraphysiological conditions (e.g. it seems to dampen exceedingly high responses to stresses). Moreover, it has been also suggested that endogenous NPY may be involved in the regulation of blood pressure and in the pathophysiology of pheochromocytomas.

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