Exocytosis from large and small dense cored vesicles in noradrenergic nerve terminals.

The noradrenergic nerve terminals and their vesicle populations have been subject to much ultrastructural research which has served to support and extend data from biochemical analysis and pharmacological-physiological experiments. Although a great deal of information has been collected, there are still many problems which need further investigation before the various aspects of large and small dense-cored vesicle function and their possible relationship to the various types of clear vesicles and vacuoles in the terminals can be fully explained. In particular, the ontogeny of microvesicles (30-40 nm), intermediate clear vesicles (45-55 nm) and large vacuoles or cisternae (150-200 nm) needs clarification before they can be fruitfully compared to similar structures assigned various roles in other types of terminals. From the data presently available the following conclusions can be drawn (Fig. 32): (1) both large and small dense-cored vesicles participate in exocytosis. (2) The various steps of the exocytotic process from vesicle fusion to vesicle membrane retrieval can be captured by ultrastructural methods but the mode(s) of membrane recapture remains to be resolved. (3) A morphologically heterogeneous population of clear vesicles probably reflects organelles of different ontogeny some being formed via terminal membrane endocytosis and some representing smooth endoplasmic reticulum or small "dense-cored" vesicles devoid of noradrenaline. (4) The small dense-cored vesicles may be formed in the cell body and transported to the terminals as this type of vesicle can be seen in the axons (where they probably are not undergoing retrograde transport as suggested for some of the small clear vesicles). Some small dense-cored vesicles may also be formed from the permanganate and dichromate-positive tubular structures common in rodent terminals. (5) There is no morphological evidence for the presence of large protein molecules such as dopamine beta-hydroxylase in the dense core of small vesicles. Their staining properties appear to reflect mainly noradrenaline and small molecules that can leak out from the vesicles in parallel with the transmitter. (6) Dopamine beta-hydroxylase and opioid peptides secreted from the noradrenergic terminals most probably originate from the large vesicles. (7) The hypothesis that only the large dense-cored vesicles contain and secrete dopamine beta-hydroxylase and opioids can help to explain the species differences in the concentrations of these substances observed in certain tissues.