Conclusions
We propose a model depicting putative signal transduction pathways underlying PACAP-induced CGA transcription and catecholamine secretion in PC12 cells (Fig 7). PACAP mediates both secretion and transcription through the PAC 1 receptor, but with quite different post-receptor signaling pathways. PACAP signals to CGA transcription through a Ca2+-independent pathway involving the CGA promoter CRE domain in cis and PKA and the transcription factor CREB in trans. PACAP-evoked secretion and transcription are subject to homologous desensitization in PC 12 cells; however, PACAP also provokes long-lasting secretion, even under dose and time circumstances where acute, DHP-sensitive secretion has been desensitized. While initial secretion is mediated by an L-type VOCC, extended secretion may involve a SOCC activated through a Gq/11/PLC-β/PI signaling pathway. Further characterization of PACAP signaling pathways will require definitive identification of the SOCC channel involved in the sustained catecholamine release.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arimura, A., and Shioda, S., 1995, Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Front. Neuroendocrinol. 16: 53–88.
Babinski, K., Bodart, V., Roy, M., De Lean, A., and Ong, H., 1996, Pituitary adenylate-cyclase activating polypeptide (PACAP) evokes long-lasting secretion and de novo biosynthesis of bovine adrenal medullary neuropeptides. Neuropeptides 30: 572–582.
Bennett, D.L., Bootman, M.D., Berridge, M.J., and Cheek, T.R., 1998, Ca2+ entry into PC12 cells initiated by ryanodine receptors or inositol 1,4,5-trisphosphate receptors. Biochem. J. 329:349–357.
Boksa, P., and Livett, B.G., 1984, Desensitization to nicotinic cholinergic agonists and K+, agents that stimulate catecholamine secretion, in isolated adrenal chromaffin cells. J. Neurochem. 42: 607–617.
Boutillier, A.L., Monnier, D., Koch, B., and Loeffler, J.P., 1994, Pituitary adenyl cyclase-activatingpeptide: a hypophysiotropic factor that stimulates proopiomelanocortin gene transcription, and proopiomelanocortin-derived peptide secretion in corticotropic cells. Neuroendocrinology 60: 493–502.
Deutsch, P.J., and Sun, Y., 1992, The 38-amino acid form of pituitary adenylate cyclase-activating polypeptide stimulates dual signaling cascades in PC12 cells and promotes neurite outgrowth. J. Biol. Chem. 267: 5108–5113.
Favre, C.J., Nüsse, O., Lew, D.P., and Krause, K.H., 1996, Store-operated Ca2+ influx: what is the message from the stores to the membrane ? J. Lab. Clin. Med. 128: 19–26.
Freedman, N.J., and Lefkowitz, R.J., 1996, Desensitization of G protein-coupled receptors. Recent Prog. Horm. Res. 51: 319–35.
Gudermann, T., Schoenberg, T., and Schultz, G., 1997, Functional and structural complexity of signal transduction via G-protein-coupled receptors. Annu. Rev. Neurosci. 20: 399–427.
Hezareh, M., Schlegel, W., and Rawlings, S.R.,1 996, PACAPand VIP stimulate Ca2+ oscillations in rat gonadotrophs through the PACAP/VIP type 1 receptor (PVRl) linked to a pertussis toxin-insensitive G-protein and the activation of phospholipase C-beta. J. Neuroendocrinol. 8: 361–374.
Iacangelo, A.L., and Eiden, L.E., 1995, Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway. Regul. Pept. 58: 65–88.
Isobe, K., Nakai, T., and Takuwa, Y., 1993, Ca2+-dependent stimulatory effect of pituitary adenylate cyclase-activating polypeptide on catecholamine secretion from cultured porcine adrenal medullary chromaffin cells. Endocrinology 132: 1757–1765.
Koizumi, S., and Inoue, K., 1998, Functional coupling of secretion and capacitative calcium entry in PC12 cells. Biochem. Biophys. Res. Commun. 247: 293–298.
Mahata, S.K., O’Connor, D.T., Mahata, M., Yoo, S.H., Taupenot, L., Wu, H., Gill, B.M., and Parmer, R.J., 1997, Novel autocrine feedback control of catecholamine release: a discrete chromogranin A fragment is a non-competitive nicotinic cholinergic antagonist. J. Clin. Invest. 100: 1623–1633.
Marley, P.D., Cheung, C.Y., Thomson, K.A., and Murphy, R., 1996, Activation of tyrosine hydroxylase by pituitary adenylate cyclase-activating polypeptide (PACAP-27) in bovine adrenal chromaffin cells. J. Auton. Nerv. Syst. 60: 141–146.
Miyata, A., Jiang, L., Stibbs, H.H., and Arimura, A., 1992, Chemical characterization of vasoactive intestinal polypeptide-like immunoreactivity in ovine hypothalamus and intestine. Regul. Pept. 38: 145–154.
Moller, K., and Sundler, F., 1996, Expression of pituitary adenylate cyclase activating peptide (PACAP) and PACAP type I receptors in the rat adrenal medulla Regul. Pept. 63:129–139.
Mouland, A.J., Bevan, S., White, J.H., and Hendy, G.N., 1994, Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression. J. Biol. Chem. 269: 6918–6926.
Muller, A., Lutz-Bucher, B., Kienlen-Campard, P., Koch, B., and Loeffler, J.P., 1998, Continuous activation of pituitary adenylate cyclase-activating polypeptide receptors elicits antipodal effects on cyclic AMP and inositol phospholipid signaling pathways in CATH.a cells: role of protein synthesis and protein kinases. J. Neurochem. 70: 1431–1440.
O’Connor, D.T., 1983, Chromogranin: widespread immunoreactivity in polypeptide hormone producing tissues and in serum. Regul. Pept. 6: 263–280.
O’Farrell, M., and Marley, P. D., 1997, Multiple calcium channels are required for pituitary adenylate cyclase-activating polypeptide-induced catecholamine secretion from bovine cultured adrenalchromaffin cells. Naunyn-Schmiedebergs Arch. Pharmacol. 356: 536–542.
Pantaloni, C., Brabet, P., Bilanges, B., Dumuis, A., Houssami, S., Spengler, D., Bockaert, J., and Joumot, L., 1996, Alternative splicing in the N-terminal extracellular domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor modulates receptor selectivity and relative potencies of PACAP-27 and PACAP-38 in phospholipase C activation. J. Biol. Chem. 271: 22146–22151.
Parmer, R.J., Xi, X.P., Wu, H. J., Helman, L. J., and Petz, L.N., 1993, Secretory protein traffic. Chromogranin A contains a dominant targeting signal for the regulated pathway. J. Clin. Invest. 92: 1042–1054.
Perrin, D., Germeshausen, A., Soling, H.D., Wuttke, W., and Jarry, H., 1995, Enhanced cAMP production mediates the stimulatory action of pituitary adenylate cyclase activating polypeptide (PACAP) on in vitro catecholamine secretion from bovine adrenal chromaffin cells. Exp. Clin. Endocrinol. Diabetes 103: 81–87.
Pisegna, J.R., and Wank, S.A., 1993, Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. Proc. Natl. Acad. Sci. USA 90: 6345–6349.
Powis, D.A., Clark, C.L., and O’Brien, K.J., 1996, Depleted internal store-activated Ca2+ entry can trigger neurotransmitter release in bovine chromaffin cells. Neurosci. Lett. 204: 165–168.
Przywara, D.A., Guo, X., Angelilli, M.L., Wakade, T.D., and Wakade, A.R., 1996, A noncholinergic transmitter, pituitary adenylate cyclase-activating polypeptide, utilizes a novel mechanism to evoke catecholamine secretion in rat adrenal chromaffin cells. J. Biol. Chem. 271: 10545–10550.
Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P.H., and Joumot, L., 1993, Differential signal transduction by five splice variants of the PACAP receptor. Nature (London) 365: 170–175.
Tanaka, K., Shibuya, I., Nagamoto, T., Yamashita, H., and Kanno, T., 1996, Pituitary adenylate cyclase-activating polypeptide causes rapid Ca2+ release from intracellular stores and long lasting Ca2+ influx mediated by Na+ influx-dependent membrane depolarization in bovine adrenal chromaffin cells. Endocrinology 137: 956–966.
Tanaka, K., Shibuya, I., Uezono, Y., Ueta, Y., Toyohira, Y., Yanagihara, N., Izumi, F., Kanno, T., and Yamashita, H., 1998, Pituitary adenylate cyclase-activating polypeptide causes Ca2+ release from ryanodine/caffeine stores through a novel pathway independent of both inositol trisphosphates andcyclic AMP inbovine adrenal medullary cells. J. Neurochem. 70: 1652–1661.
Tang, K., Wu, H., Mahata S.K., Taupenot, L., Rozansky, D.J., Parmer, R.J., and O’Connor, D.T., 1996, Stimulus-transcription coupling in pheochromocytoma cells. Promoter region-specific activation of chromogranin a biosynthesis. J. Biol. Chem. 271: 28382–28390.
Taupenot, L., Mahata, M., Mahata, S. K. and O’Connor, D. T., 1999. Time-dependent effects of the neuropeptide PACAP.on catecholamine secretion: stimulation and desensitization. Hypertension 34: 1152–1162.
Taupenot, L., Mahata, S.K., Wu, H., and O’ Connor, D.T., 1998, Peptidergic stimulation of secretion and transcription in chromaffin cells: cis and trans signaling determinants of pituitary adenylyl cyclase-activating polypeptide (PACAP). J. Clin. Invest. 101: 863–876.
Videen, J.S., Mezger, M.S., Chang, Y.M., and O’Connor, D.T., 1992, Calcium and catecholamine interactions with adrenal chromogranins. Comparison of driving forces in binding and aggregation. J. Biol. Chem. 267: 3066–3073.
Walton, K.M., Rehfuss, R.P., Chrivia, J.C., Lochner, J.E., and Goodman, R.H., 1992, A dominant repressor of cyclic adenosine 3’,5’-monophosphate (cAMP)-regulated enhancer-binding protein activity inhibits the CAMP-mediated induction of the somatostatin promoter in vivo. Mol. Endocrinol. 6: 647–655.
Widnell, K.L., Chen, J.S., Iredale, P.A., Walker, W.H., Duman, R.S., Habener, J.F., and Nestler, E.J., 1996, Transcriptional regulation of CREB (cyclic AMP response element-binding protein) expression in CATH.a cells. J. Neurochern. 66: 1770–1773.
Wu, H., Mahata S.K., Mahata, M., Webster, N.J., Parmer, R. J., and O’Connor, D.T., 1995, A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A. J. Clin. Invest. 96: 568–578.
Wu, H.J., Rozansky, D.J., Parmer, R.J., Gill, B.M. and O’Connor, D.T., 1991, Structure and function of the chromogranin A gene. Clues to evolution and tissue-specific expression. J. Biol. Chem. 266: 13130–13134.
Yoo, S.H., and Albanesi, J.P., 1991, High capacity, low affinity Ca2+ binding of chromogranin A. Relationship between the pH-induced conformational change and Ca2+ binding property. J. Biol. Chem. 266: 7740–7745.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Kluwer Academic Publishers
About this chapter
Cite this chapter
Taupenot, L., Mahata, M., Mahata, S.K., Wu, H., O’Connor, D.T. (2002). Regulation of Chromogranin a Transcription and Catecholamine Secretion by the Neuropeptide Pacap. In: Helle, K.B., Aunis, D. (eds) Chromogranins. Advances in Experimental Medicine and Biology, vol 482. Springer, Boston, MA. https://doi.org/10.1007/0-306-46837-9_7
Download citation
DOI: https://doi.org/10.1007/0-306-46837-9_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-46446-1
Online ISBN: 978-0-306-46837-7
eBook Packages: Springer Book Archive