The adrenal medulla: a model for studies of hormonal and neuronal storage and release mechanisms.

We have observed that phospholipids and protein of the catecholamine (CA) storage granules, i.e. the chromaffin granules, interact in an in vitro system to form liposomal particles, which in many respects resemble the intact matrix of the bovine chromaffin granule. A model has been suggested which consists of an aqueous phase, containing the acidic chromogranins and intact dopamine-beta-hydroxylase (DBH) ATP and CA, embedded in a liquid crystal of the matrix phospholipids. Ca2+ may play a significant role in the sequence of functional transitions of such an organelle, not only in the accumulation of Ca2+, as during the secretory phase of the intact cell, but also as the agent inducing a separation of the outer membrane bilayer from the matrix phase to be released, as during exocytosis. Furthermore, a liposome model of the matrix may also tentatively explain the occurrence of intact matrices in the interstitium of stimulated glands. Recent evidence for the identity between chromogranin A and DBH subunits have been summarized and a possible role for the inactive subunits in the ionic binding of ATP and CA in the aqueous phase of the matrix is discussed. A role of Ca2+ and cyclic AMP in the mediation of beta-adrenergic modulation is postulated on the basis of our recent work on acetylcholine-induced release of CA from perfused and stimulated bovine adrenals. We conclude that such a beta-adrenergic modulation is secondary to that of the cholinergic response. Hence, this activation is able to enhance the output induced by mild cholinergic stimulation although insufficient to evoke a CA release by itself.