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Neuropeptides, Growth Factors, and Cytokines: A Cohort of Informational Molecules Whose Expression Is Up-Regulated by the Stress-Associated Slow Transmitter PACAP in Chromaffin Cells

Cellular and Molecular Neurobiology volume 30, pages 1441–1449 (2010)Cite this article

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a co-transmitter with acetylcholine at the adrenomedullary synapse, mediating sustained hormone secretion and regulation of cellular plasticity in response to stress at the level of gene transcription. Here we have extended our investigation of PACAP-regulated neuroendocrine cell-specific genes from PC12 cells to PC12 cells expressing physiological levels of the PAC1hop receptor found on chromaffin cells in vivo. PACAP induces in these PC12_bPAC1hop cells an additional cohort of genes, compared to PC12 cells, enriched in informational molecules including cytokines, neuropeptides, and growth factors. Using two newly developed microarray platforms for expressed bovine transcripts, we further examined PACAP-induced genes in bovine chromaffin cells during a period of exposure (6 h) corresponding to a period of prolonged metabolic or psychogenic stress in vivo during which PACAP is released from the splanchnic nerve onto chromaffin cells. As in PC12_bPAC1hop cells, PACAP induced in bovine chromaffin cells a cohort of genes encoding secretory proteins, identified by tiling for cellular localization using Ingenuity Pathway Analysis, which were highly enriched in informational molecules (secreted proteins acting at extracellular receptors). These included cytokines, growth factors and hormones, as well as converting enzymes, or protease inhibitors modulating converting enzyme function. Several neuropeptide prohormone transcripts not previously shown to be PACAP-regulated in chromaffin cells, such as thyrotropin-releasing hormone, and tachykinin precursor 1, were identified. Identification of this cohort of informational molecule-encoding transcripts suggests a wider, more integrative role for PACAP as a co-transmitter specific to stress transduction in the adrenal medulla.

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Acknowledgments

The authors wish to thank Dr Abdel G. Elkahloun [National Human Genome Research Institute, National Institutes of Health (NIH)] for performing microarray experiments and Ms. Chang-Mei Hsu for expert technical assistance in preparation of chromaffin cell cultures, and the NIMH Intramural Research Program for support of Project 1ZO1-MH002386-21-23.

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Affiliations

  1. Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Building 49, Room 5A-38, Bethesda, MD, 20892, USA

    Djida Ait-Ali

  2. Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD, 20892, USA

    Babru Samal, Tomris Mustafa & Lee E. Eiden

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  1. Djida Ait-Ali
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  2. Babru Samal
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  3. Tomris Mustafa
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  4. Lee E. Eiden
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Correspondence to Djida Ait-Ali.

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A commentary to this article can be found at doi:10.1007/s10571-010-9607-8.

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Ait-Ali, D., Samal, B., Mustafa, T. et al. Neuropeptides, Growth Factors, and Cytokines: A Cohort of Informational Molecules Whose Expression Is Up-Regulated by the Stress-Associated Slow Transmitter PACAP in Chromaffin Cells. Cell Mol Neurobiol 30, 1441–1449 (2010). https://doi.org/10.1007/s10571-010-9620-y

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Keywords

  • Adrenal medulla
  • Chromaffin cell
  • Cytokine
  • Growth factor
  • Hormone
  • Microarray
  • Neuropeptide
  • PACAP
  • PC12
  • Stress