Long term stimulation changes the vesicular monoamine transporter content of chromaffin granules

J Biol Chem. 1995 Jul 7;270(27):16030-8. doi: 10.1074/jbc.270.27.16030.


Bovine chromaffin cells cultured for 5 days in the presence of depolarizing concentrations of K+ ions show a decreased number of secretory (chromaffin) granules per cell. These cells were still capable of exocytosis. Their contents in catecholamine and chromogranin A, components of the granule matrix, and cytochrome b561, a major protein of the granule membrane, were decreased to 35, 30, and 50% of control cells, respectively. However, in the same cells, the number of [3H]dihydrotetrabenazine binding sites, a specific ligand of the vesicular monoamine transporter, was increased to 180% of controls. In situ uptake of noradrenaline in permeabilized cells indicated that [3H]dihydrotetrabenazine binding sites were associated with a functional vesicular monoamine transporter. When analyzed by isopycnic centrifugation, these sites cosedimented with catecholamine, chromogranin A, and cytochrome b561, in a peak with a density lighter than that from controls. The composition of this peak suggests that it contains incompletely matured secretory granules, with a 3-5-fold increase in the vesicular monoamine transporter content of this membrane. This increase might indicate that an adaptative process occurs which allows a faster filling of the granules in continuously secreting cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Catecholamines / metabolism
  • Cattle
  • Cell Fractionation
  • Cell Membrane Permeability
  • Cells, Cultured
  • Chromaffin Granules / metabolism*
  • Chromaffin System / cytology
  • Chromaffin System / ultrastructure
  • Chromogranin A
  • Chromogranins / isolation & purification
  • Cytochrome b Group / analysis
  • Exocytosis
  • Fluorescent Antibody Technique
  • Glycoproteins / metabolism*
  • Intracellular Membranes / metabolism*
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Neuropeptides*
  • Norepinephrine / metabolism
  • Potassium / pharmacology
  • Stimulation, Chemical
  • Tetrabenazine / analogs & derivatives
  • Tetrabenazine / metabolism
  • Tyrosine 3-Monooxygenase / isolation & purification
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins


  • Catecholamines
  • Chromogranin A
  • Chromogranins
  • Cytochrome b Group
  • Glycoproteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Neuropeptides
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • cytochrome b561
  • dihydrotetrabenazine
  • Tyrosine 3-Monooxygenase
  • Potassium
  • Norepinephrine
  • Tetrabenazine