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

Bhavani Shankar Sahu, Sumana Mahata, Keya Bandyopadhyay, Manjula Mahata, Ennio Avolio, Teresa Pasqua, Chinmayi Sahu, Gautam K. Bandyopadhyay, Alessandro Bartolomucci, Nicholas J.G. Webster, Geert Van Den Bogaart, Reiner Fischer-Colbrie, Angelo Corti, Lee E. Eiden, Sushil K. Mahata

Research output: Contribution to journalArticle

Abstract

We have previously shown that the chromogranin A (CgA)-derived peptide catestatin (CST: hCgA 352–372 ) 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 3 H‐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.

Original languageEnglish
Pages (from-to)51-70
Number of pages20
JournalCell and Tissue Research
Volume376
Issue number1
DOIs
Publication statusPublished - Apr 3 2019

Keywords

  • Catecholamine
  • Catestatin
  • Chromaffin vesicles
  • Nicotine
  • PACAP
  • PC12 cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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  • Cite this

    Sahu, B. S., Mahata, S., Bandyopadhyay, K., Mahata, M., Avolio, E., Pasqua, T., Sahu, C., Bandyopadhyay, G. K., Bartolomucci, A., Webster, N. J. G., Van Den Bogaart, G., Fischer-Colbrie, R., Corti, A., Eiden, L. E., & Mahata, S. K. (2019). Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells. Cell and Tissue Research, 376(1), 51-70. https://doi.org/10.1007/s00441-018-2956-1