Noradrenaline storing vesicles in sympathetic neurons and their role in neurotransmitter release: an historical overview of controversial issues.

More than 25 years have passed since the original demonstration that proteins such as chromogranin A and dopamine-beta-hydroxylase, which are co-stored together with noradrenaline in large dense cored vesicles in adrenergic nerves, are released by exocytosis. Despite much evidence in favour, it was for a long time thought that large dense cored vesicles were not eminently involved in the release of noradrenaline. The present review attempts to demonstrate, making use of evidence from different approaches, that the release of noradrenaline from sympathetic neurons occurs ultimately from large dense cored vesicles. A model of the secretory cycle is proposed.