Mechanisms of catecholamine accumulation in adrenal chromaffin granules

Two different process seem to be involved in the storage of CA in adrenal chromaffin granules, an Mg 2+ /ATP-dependent active mechanism operating at the level of the granular membrane and involving ATPase and an intragranular interaction of the CA with nucleotides such as ATP and also with chromogranins.

Abstract

According to the above findings, two different process seem to be involved in the storage of CA in adrenal chromaffin granules. The amines are apparently pumped into the organelles by an Mg2+/ATP-dependent active mechanism operating at the level of the granular membrane and involving ATPase. This mechanism alone is hardly responsible for the very high content of CA normally present in chromaffin granules. Previous experiments have shown that the maximum noradrenaline concentration reached in isolated granular membranes as a consequence of an active transport amounts to 5 mM (see ref. 1). However, the CA concentration in intact chromaffin granules was calculated to be approximately 500 mM. The buildup of this high concentration is most likely due to the existence of the second mechanism,i.e. the intragranular interaction of the CA with nucleotides such as ATP (which probably preexists in the granules before the amines are stored) and also with chromogranins. This interaction probably reduces the diffusion of CA out of the granules enabling the amine pump to operate against a much higher amine concentration gradient. Preliminary experiments with artificial lipid membranes confirm this view, since addition of ATP and CaCl2 to noradrenaline or adrenaline solutions decreases the velocity of membrane permeation of the amines probably as a result of a reduction of the concentration of non-aggregated amine. On the other hand, the binding of CA in the organelles is of a dynamic nature and rather loose as indicated by the fluorescence measurements. This reversibility of the storage process allows to be rapidly liberated,e.g. during the release process of CA. The two mechanisms are summarized in Fig. 7 which is a hypothetical model demonstrating the mode of storage of catecholamines in adrenal chromaffin granules.