Transport of monoamines in membranes of adrenal chromaffin granules: physiological and pharmacological aspects.

The membranes of isolated bovine adrenal chromaffin granules take up catecholamines by an ATP-dependent process which fulfills many criteria of a carriermediated energy-requiring transport. This transport together with an intragranular mechanism probably explains the high storage capacity of the chromaffin granules for catecholamines. 5.2 Other amines (e.g. 5-hydroxytryptamine (5HT), octopamine) are also taken up by the membranes, but to a different degree. This probably explains why amines normally not present in storage organelles, if available in increased amounts, may accumulate within these organelles and function as false neurohumoral transmitters. 5.3. Two mechanisms of amine uptake seem to exist at the level of the granule membranes, one reserpine-sensitive (transporting, for instance, catecholamines and 5HT), and one reserpine-resistant (transporting tryptamine and partly metaraminol). Both mechanisms depend on ATP. 5.4. Chlorpromazine interferes with the reserpine-sensitive as well as the reserpine-resistant uptake of noradrenaline (NA) by granule membranes to a similar degree. Consequently the mechanism of action of neuroleptics and reserpine at the granule membrane level are probably different. 5.5. There is only an incomplete parallelism between the inhibition of NA-uptake by granule membranes in vitro and the degree of enhancement of neuronal DA turnover in vivo caused by various neuroleptics. Therefore, factors other than interference with the amine transport through the granule membranes must be co-determinant in the neuroleptic induced enhancement of DA turnover in vivo.