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Vesicular Monoamine Transporters (VMATs) in Adrenal Chromaffin Cells: Stress-Triggered Induction of VMAT2 and Expression in Epinephrine Synthesizing Cells

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Abstract

Vesicular monoamine transporters (VMATs) mediate transmitter uptake into neurosecretory vesicles. There are two VMAT isoforms, VMAT1 and VMAT2, encoded by separate genes and displaying different cellular distributions and pharmacological properties. We examined the effect of immobilization stress (IMO) on expression of VMATs in the rat adrenal medulla. Under basal conditions, VMAT1 is widely expressed in all adrenal chromaffin cells, while VMAT2 is co-localized with tyrosine hydroxylase (TH) but not phenylethanolamine N-methyltransferase (PNMT), indicating its expression in norepinephrine (NE)-, but not epinephrine (Epi)-synthesizing chromaffin cells. After exposure to IMO, there was no change in levels of VMAT1 mRNA. However, VMAT2 mRNA was elevated after exposure of rats to 2 h IMO once (1× IMO) or daily for 6 days (6× IMO). The changes in VMAT2 mRNA were reflected by increased VMAT2 protein after the repeated IMO. Immunofluorescence revealed an increased number of cells expressing VMAT2 following repeated IMO and its colocalization with PNMT in many chromaffin cells. The findings suggest an adaptive mechanism in chromaffin cells whereby enhanced catecholamine storage capacity facilitates more efficient utilization of the well-characterized heightened catecholamine biosynthesis with repeated IMO stress.

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References

  • Cannon W (1929) Organization of physiological homeostasis. Physiol Rev 9:3431–3900

    Google Scholar 

  • Catlow K, Ashurst HL, Varro A, Dimaline R (2007) Identification of a gastrin response element in the vesicular monoamine transporter type 2 promoter and requirement of 20 S proteasome subunits for transcriptional activity. J Biol Chem 282:17069–17077

    Article  CAS  PubMed  Google Scholar 

  • Erickson JD, Eiden LE, Hoffman BJ (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci USA 89:10993–10997

    Article  CAS  PubMed  Google Scholar 

  • Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci USA 93:5166–5171

    Article  CAS  PubMed  Google Scholar 

  • Gerhard M, Neumayer N, Presecan-Siedel E, Zanner R, Lengyel E, Cramer T, Hocker M, Prinz C (2001) Gastrin induces expression and promoter activity of the vesicular monoamine transporter subtype 2. Endocrinology 142:3663–3672

    Article  CAS  PubMed  Google Scholar 

  • Hansson SR, Mezey E, Hoffman BJ (1998) Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2. II. Expression in neural crest derivatives and their target sites in the rat. Brain Res 110:159–174

    Article  CAS  Google Scholar 

  • Henry JP, Botton D, Sagne C, Isambert MF, Desnos C, Blanchard V, Raisman-Vozari R, Krejci E, Massoulie J, Gasnier B (1994) Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules. J Exp Biol 196:251–262

    CAS  PubMed  Google Scholar 

  • Holtje M, von Jagow B, Pahner I, Lautenschlager M, Hortnagl H, Nurnberg B, Jahn R, Ahnert-Hilger G (2000) The neuronal monoamine transporter VMAT2 is regulated by the trimeric GTPase Go. J Neurosci 20:2131–2141

    CAS  PubMed  Google Scholar 

  • Johnson GRJ (1988) Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport. Physiol Rev 68:232–307

    CAS  PubMed  Google Scholar 

  • Kanner BI, Schuldiner S (1987) Mechanism of transport and storage of neurotransmitters. CRC Crit Rev Biochem 22:1–38

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, Mikulaj L (1970) Adrenal and urinary catecholamines in rats during adaptation to repeated immobilization stress. Endocrinology 87:738–743

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, Weise VK, Kopin IJ (1970) Elevation of adrenal tyrosine hydroxylase and phenylethanolamine-N-methyl transferase by repeated immobilization of rats. Endocrinology 87:744–749

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, Goldstein DS, Weise VK, Holmes C, Szemeredi K, Bagdy G, Kopin IJ (1992) Effects of handling or immobilization on plasma levels of 3,4-dihydroxyphenylalanine, catecholamines, and metabolites in rats. J Neurochem 58:2296–2302

    Article  CAS  PubMed  Google Scholar 

  • Kvetnansky R, Sabban EL, Palkovits M (2009) Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89:535–606

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Peter D, Roghani A, Schuldiner S, Prive GG, Eisenberg D, Brecha N, Edwards RH (1992) A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70:539–551

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Kvetnansky R, Serova L, Sollas A, Sabban EL (2005) Increased susceptibility to transcriptional changes with novel stressor in adrenal medulla of rats exposed to prolonged cold stress. Brain Res Mol Brain Res 141:19–29

    Article  CAS  PubMed  Google Scholar 

  • Nankova B, Kvetnansky R, McMahon A, Viskupic E, Hiremagalur B, Frankle G, Fukuhara K, Kopin IJ, Sabban EL (1994) Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress. Proc Natl Acad Sci USA 91:5937–5941

    Article  CAS  PubMed  Google Scholar 

  • Peter D, Jimenez J, Liu Y, Kim J, Edwards RH (1994) The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem 269:7231–7237

    CAS  PubMed  Google Scholar 

  • Peter D, Liu Y, Sternini C, de Giorgio R, Brecha RN, Edwards RH (1995) Differential expression of two vesicular monoamine transporters. J Neurosci 15:6179–6188

    CAS  PubMed  Google Scholar 

  • Rusnak M, Kvetnansky R, Jelokova J, Palkovits M (2001) Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats. Brain Res 899:20–35

    Article  CAS  PubMed  Google Scholar 

  • Sabban EL, Kvetnansky R (2001) Stress-triggered activation of gene expression in catecholaminergic systems: dynamics of transcriptional events. Trends Neurosci 24:91–98

    Article  CAS  PubMed  Google Scholar 

  • Schutz B, Schafer MK, Eiden LE, Weihe E (1998) Vesicular amine transporter expression and isoform selection in developing brain, peripheral nervous system and gut. Brain Res Dev Brain Res 106:181–204

    Article  CAS  PubMed  Google Scholar 

  • Weihe E, Eiden LE (2000) Chemical neuroanatomy of the vesicular amine transporters. FASEB J 14:2435–2449

    Article  CAS  PubMed  Google Scholar 

  • Weihe E, Schafer MK, Erickson JD, Eiden LE (1994) Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat. J Mol Neurosci 5:149–164

    Article  CAS  PubMed  Google Scholar 

  • Wong DL, Tank AW (2007) Stress-induced catecholaminergic function: transcriptional and post-transcriptional control. Stress 10:121–130

    Article  CAS  PubMed  Google Scholar 

  • Zucker M, Weizman A, Rehavi M (2005) Repeated swim stress leads to down-regulation of vesicular monoamine transporter 2 in rat brain nucleus accumbens and striatum. Eur Neuropsychopharmacol 15:199–201

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge support from NIH grant NS28869, Slovak Grant Agency APVV-0148-06 and VEGA2/0133/08.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA

    Andrej Tillinger, Anne Sollas, Lidia I. Serova & Esther L. Sabban

  2. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic

    Richard Kvetnansky

Authors
  1. Andrej Tillinger
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  2. Anne Sollas
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  3. Lidia I. Serova
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  4. Richard Kvetnansky
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  5. Esther L. Sabban
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Corresponding author

Correspondence to Esther L. Sabban.

Additional information

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

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Tillinger, A., Sollas, A., Serova, L.I. et al. Vesicular Monoamine Transporters (VMATs) in Adrenal Chromaffin Cells: Stress-Triggered Induction of VMAT2 and Expression in Epinephrine Synthesizing Cells. Cell Mol Neurobiol 30, 1459–1465 (2010). https://doi.org/10.1007/s10571-010-9575-z

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  • DOI: https://doi.org/10.1007/s10571-010-9575-z

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