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

  • Bhavani Shankar SahuEmail author
  • 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. MahataEmail author
Regular Article


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.


Chromaffin vesicles Catecholamine PC12 cells Nicotine PACAP Catestatin 



The electron micrographs were taken in the Cellular and Molecular Medicine Electron microscopy core facility at UCSD, which is supported in part by National Institutes of Health Award number S10OD023527. This research was supported by a grant from the Department of Veterans Affairs (I01BX000323 to S.K.M.; I01BX002709 and an SRCS award to N.J.G.W) and the National Institutes of Health (NIH/NIDDK DK102496 to A.B. and MH002386 to L.E.E.). JCSTF-180217 travelling research fellowship to B.S.S. from company of biologists (Cambridge, UK). The Noland Scholarship from the California Institute of Technology supported S.M.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Bhavani Shankar Sahu
    • 1
    • 2
    Email author
  • Sumana Mahata
    • 3
  • Keya Bandyopadhyay
    • 2
  • Manjula Mahata
    • 2
  • Ennio Avolio
    • 4
  • Teresa Pasqua
    • 4
  • Chinmayi Sahu
    • 1
  • Gautam K. Bandyopadhyay
    • 2
  • Alessandro Bartolomucci
    • 1
  • Nicholas J. G. Webster
    • 2
    • 5
  • Geert Van Den Bogaart
    • 6
  • Reiner Fischer-Colbrie
    • 7
  • Angelo Corti
    • 8
  • Lee E. Eiden
    • 9
  • Sushil K. Mahata
    • 2
    • 5
    Email author
  1. 1.Department of Integrative Biology and PhysiologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of MedicineUniversity of California, San DiegoLa JollaUSA
  3. 3.California Institute of TechnologyPasadenaUSA
  4. 4.University of CalabriaCosenzaItaly
  5. 5.VA San Diego Healthcare SystemSan DiegoUSA
  6. 6.Department of Molecular ImmunologyUniversity of GroningenGroningenNetherlands
  7. 7.Department of PharmacologyMedical University of InnsbruckInnsbruckAustria
  8. 8.IRCCS San Raffaele Scientific InstituteSan Raffaele Vita-Salute UniversityMilanItaly
  9. 9.Section on Molecular Neuroscience, NIMH-IRPBethesdaUSA

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