Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells

Cell Tissue Res. 2019 Apr;376(1):51-70. doi: 10.1007/s00441-018-2956-1. Epub 2018 Nov 22.


We have previously shown that the chromogranin A (CgA)-derived peptide catestatin (CST: hCgA352-372) inhibits nicotine-induced secretion of catecholamines from the adrenal medulla and chromaffin cells. In the present study, we seek to determine whether CST regulates dense core (DC) vesicle (DCV) quanta (catecholamine and chromogranin/secretogranin proteins) during acute (0.5-h treatment) or chronic (24-h treatment) cholinergic (nicotine) or peptidergic (PACAP, pituitary adenylyl cyclase activating polypeptide) stimulation of PC12 cells. In acute experiments, we found that both nicotine (60 μM) and PACAP (0.1 μM) decreased intracellular norepinephrine (NE) content and increased 3H-NE secretion, with both effects markedly inhibited by co-treatment with CST (2 μM). In chronic experiments, we found that nicotine and PACAP both reduced DCV and DC diameters and that this effect was likewise prevented by CST. Nicotine or CST alone increased expression of CgA protein and together elicited an additional increase in CgA protein, implying that nicotine and CST utilize separate signaling pathways to activate CgA expression. In contrast, PACAP increased expression of CgB and SgII proteins, with a further potentiation by CST. CST augmented the expression of tyrosine hydroxylase (TH) but did not increase intracellular NE levels, presumably due to its inability to cause post-translational activation of TH through serine phosphorylation. Co-treatment of CST with nicotine or PACAP increased quantal size, plausibly due to increased synthesis of CgA, CgB and SgII by CST. We conclude that CST regulates DCV quanta by acutely inhibiting catecholamine secretion and chronically increasing expression of CgA after nicotinic stimulation and CgB and SgII after PACAPergic stimulation.

Keywords: Catecholamine; Catestatin; Chromaffin vesicles; Nicotine; PACAP; PC12 cells.

MeSH terms

  • Animals
  • Catecholamines / metabolism*
  • Chromogranin A / pharmacology
  • Chromogranin A / physiology*
  • Chromogranins / metabolism*
  • Glycoprotein Hormones, alpha Subunit / metabolism
  • Humans
  • Nicotine / pharmacology*
  • Norepinephrine / metabolism
  • PC12 Cells
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology*
  • Rats
  • Seminal Vesicle Secretory Proteins / metabolism
  • Signal Transduction / drug effects
  • Tyrosine 3-Monooxygenase / metabolism


  • Catecholamines
  • Chromogranin A
  • Chromogranins
  • Glycoprotein Hormones, alpha Subunit
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Seminal Vesicle Secretory Proteins
  • chromogranin A (344-364)
  • Nicotine
  • Tyrosine 3-Monooxygenase
  • Norepinephrine