Time required for transmitter accumulation inside monoaminergic storage vesicles differs in peripheral and in central systems

Monoamine storage vesicles accumulate transmitters via an active transport process which presents similar pharmacological and bioenergetic properties in all monoaminergic systems. Using [ 3H]reserpine, a specific ligand of the vesicular monoamine transporter on isolated storage vesicles, we have determined the molecular turnover number of the monoamine transporter and found in various monoaminergic systems an identical value of 135 molecules of substrate transported per min. Using high performance liquid chromatography-electrochemical monoamine determination and the binding of [ 3H]dihydrotetrabenazine, a specific ligand of the vesicular monoamine transporter in tissue homogenates, we have measured the ratio of transmitter molecules per transporter in various rat tissues containing high amounts of monoamines. This ratio is about 500 in brain regions (striatum, hypothalamus, midbrain) and in the maxillary gland, it varies from 2000 to 7000 in sympathetic nerve terminals in the heart, brown adipose tissue and vas deferens, and it is 6000 in platelets and 280,000 in the adrenal medulla. The minimal time required in vivo for biogenic amine accumulation inside storage vesicles could be derived from these data. Values of 2–4 min were found for brain or maxillary gland synaptic vesicles, 15–50 min for heart, brown adipose tissue or vas deferens sympathetic vesicles and for platelet granules, and 35 h for adrenal medulla chromaffin granules. Thus the maturation time of monoaminergic vesicles, in terms of monoamine accumulation, is highly variable, being short in the brain and maxillary glands, 5–20-fold longer in the sympathetic nervous system and in platelets, and much increased in adrenals. These differences may be related to the character and function of each secretion: recycling and re-use of vesicles after exocytosis may have a more important physiological role in central synapses than at the periphery or in endocrine secretion.