Neurons, Chromaffin Cells and Membrane Fusion - Fusion of Biological Membranes and Related Problems - page 324

classical neurotransmitters such as ACh, glutamate and GABA are stored
in, and released from, the SSVs (for review see De Camilli and Jahn,
1990). These vesicles originate from the endosomal compartment (Régnier-
Vigouroux and Huttner, 1993) and are continuously regenerated by local
recycling. The neuropeptides, on the other hand, are stored in, and released
from, the LDVs (Winkler and Fischer-Colbrie, 1990). Intensive work on
SSVs has led to a good insight in their biogenesis and a better under-
standing of the molecular mechanisms underlying vesicle recycling, such
that a first glimpse of the exocytosis/endocytosis cycle is starting to emerge.
For an extensive view on characteristics of SSVs as well as the SSV-cycle,
the reader is referred to other excellent reviews in this volume. In this
review we want to focus on the biochemical properties and the intraneu-
ronal dynamics of LDVs of noradrenergic neurons and the-quite similar-
secretory granules of the chromaffin cells.
In 1953 it was demonstrated by Blascko and Welch that in the
adrenal medulla catecholamines were stored in subcellular organelles
called chromaffin granules. Further research revealed that these gran-
ules contain specific soluble proteins, the chromogranins (see Kirschner
and Kirschner, 1971) and membrane proteins (see Winkler, 1971).
Biochemical and immunochemical studies directly led to the finding
that, upon stimulation of the adrenal medulla these chromogranins are
released by the mechanism of exocytosis (see Kirschner and Kirschner,
1971).
Although it was already proposed by Scott in 1905 that “nerves act
upon one another and other cells by the passage of a chemical substance
of the nature of a ferment or proferment” in other words by secretion of
an enzyme or a protein, it was only in 1969 that, in analogy with the chro-
maffin cells, also (splenic) nerves were actually shown to secrete proteins.
The proteins, chromogranin A and the soluble form of the enzyme
dopamine ß-hydroxylase (DbH), present in the LDVs, were shown to be
released upon stimulation from sympathetic neurons together with nora-
drenaline (NA), while the enzymes tyrosine hydroxylase and lactate-
dehydrogenase, present in the cytoplasm, were not released (De Potter et
al., 1969; Smith et al., 1970). Despite these important findings, LDVs were
considered for many years to be of little physiological importance and not
eminently involved in chemical neurotransmission (Basbeum and Heuser,
1979; Pollard et al., 1982). It was only after the demonstration of the pres-
ence of peptides as NPY and enkephalins in LDVs and consequently their
co-release with NA, that the interest in LDVs was renewed (Lundberg and
Hockfelt, 1983; Lundberg et al., 1989). Further studies led to the concept of
differential release from which it was inferred that LDVs release their