Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice

Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):162-7. doi: 10.1073/pnas.97.1.162.

Abstract

The recent availability of mice lacking the neuronal form of the vesicular monoamine transporter 2 (VMAT2) affords the opportunity to study its roles in storage and release. Carbon fiber microelectrodes were used to measure individual secretory events of histamine and 5-hydroxytryptamine (5-HT) from VMAT2-expressing mast cells as a model system for quantal release. VMAT2 is indispensable for monoamine storage because mast cells from homozygous (VMAT2(-/-)) mice, while undergoing granule-cell fusion, do not release monoamines. Cells from heterozygous animals (VMAT2(+/-)) secrete lower amounts of monoamine per granule than cells from wild-type controls. Investigation of corelease of histamine and 5-HT from granules in VMAT2(+/-) cells revealed 5-HT quantal size was reduced more than that of histamine. Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Electrochemistry
  • Exocytosis
  • Fluorescent Antibody Technique
  • Histamine / metabolism*
  • Mast Cells / metabolism*
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Knockout
  • Microelectrodes
  • Neuropeptides*
  • Ruthenium Red
  • Serotonin / metabolism*
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins

Substances

  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Neuropeptides
  • Slc18a2 protein, mouse
  • Vesicular Biogenic Amine Transport Proteins
  • Vesicular Monoamine Transport Proteins
  • Ruthenium Red
  • Serotonin
  • Histamine