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Intravesicular Factors Controlling Exocytosis in Chromaffin Cells

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Abstract

Chromaffin granules are similar organelles to the large dense core vesicles (LDCV) present in many secretory cell types including neurons. LDCV accumulate solutes at high concentrations (catecholamines, 0.5–1 M; ATP, 120–300 mM; or Ca2+, 40 mM (Bulenda and Gratzl Biochemistry 24:7760–7765, 1985). Solutes seem to aggregate to a condensed matrix to elude osmotic lysis. The affinity of solutes for LDCV matrix is responsible for the delayed release of catecholamines during exocytosis. The aggregation of solutes occurs due to a specific H+ pump denominated V-ATPase that maintains an inner acidic media (pH ≈5.5). This pH gradient against cytosol is also responsible for the vesicular accumulation of amines and Ca2+. When this gradient is reduced by modulation of the V-ATPase activity, catecholamines and Ca2+ are moved toward the cytosol. In addition, some drugs largely accumulate inside LDCV and not only impair the accumulation of natural solutes, but also act as false neurotransmitters when they are co-released with catecholamines. There is much experimental evidence to conclude that the physiological modulation of vesicle pH and the manipulation of intravesicular media with drugs affect the LDCV cargo and change the kinetics of exocytosis. Here, we will present some experimental data demonstrating the participation of drugs in the kinetics of exocytosis through changes in the composition of vesicular media. We also offer a model to explain the regulation of exocytosis by the intravesicular media that conciliate the experimentally obtained data.

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Fig. 1

Abbreviations

Cgs:

Chromogranins

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Authors and Affiliations

  1. Unit of Pharmacology, Medical School, La Laguna University, 38071, La Laguna, Tenerife, Spain

    Ricardo Borges, Daniel Pereda, Beatriz Beltrán, Margarita Prunell, Miriam Rodríguez & José D. Machado

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  1. Ricardo Borges
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  2. Daniel Pereda
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  3. Beatriz Beltrán
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  4. Margarita Prunell
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  5. Miriam Rodríguez
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  6. José D. Machado
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Correspondence to Ricardo Borges.

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A commentary to this article can be found at doi:10.1007/s10571-010-9610-0.

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Borges, R., Pereda, D., Beltrán, B. et al. Intravesicular Factors Controlling Exocytosis in Chromaffin Cells. Cell Mol Neurobiol 30, 1359–1364 (2010). https://doi.org/10.1007/s10571-010-9589-6

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