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

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Abstract

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.

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Acknowledgments

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.

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  1. Bhavani Shankar Sahu and Sumana Mahata contributed equally to this work.

Authors and Affiliations

  1. Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA

    Bhavani Shankar Sahu, Chinmayi Sahu & Alessandro Bartolomucci

  2. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0732, USA

    Bhavani Shankar Sahu, Keya Bandyopadhyay, Manjula Mahata, Gautam K. Bandyopadhyay, Nicholas J. G. Webster & Sushil K. Mahata

  3. California Institute of Technology, Pasadena, CA, USA

    Sumana Mahata

  4. University of Calabria, Cosenza, Italy

    Ennio Avolio & Teresa Pasqua

  5. VA San Diego Healthcare System, San Diego, CA, USA

    Nicholas J. G. Webster & Sushil K. Mahata

  6. Department of Molecular Immunology, University of Groningen, Groningen, Netherlands

    Geert Van Den Bogaart

  7. Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria

    Reiner Fischer-Colbrie

  8. IRCCS San Raffaele Scientific Institute, San Raffaele Vita-Salute University, Milan, Italy

    Angelo Corti

  9. Section on Molecular Neuroscience, NIMH-IRP, Bethesda, MD, USA

    Lee E. Eiden

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  1. Bhavani Shankar Sahu
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Correspondence to Bhavani Shankar Sahu or Sushil K. Mahata.

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Sahu, B.S., Mahata, S., Bandyopadhyay, K. et al. Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells. Cell Tissue Res 376, 51–70 (2019). https://doi.org/10.1007/s00441-018-2956-1

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