The kinetics of adrenal catecholamine secretion elicited by splanchnic nerve stimulation or by Ach is consistent with non-exocytotic, multivesicular release on cation exchange basis.

In eight anaesthetized cats, one dog and one pig the left adrenal was activated during a 5-15-min period by splanchnic nerve stimulation (10-30 V, 0.2-2 ms) at supramaximal frequencies (10-50 Hz) or by i.a. infusion of acetylcholine in high concentration (10(-4) M). The catecholamine (CA) release, as recorded in the adrenal venous outflow, was characterized by a very steep rise to a peak (within less than 10 s), followed by a rapid decline which after 5-10 min continued as a 'steady state' secretion, still above prestimulatory level. The initial release curve satisfied the straight line equation log B = K square root (sigma ml) + log Bmax, shown previously by us to be characteristic of the cation-induced amine release from amine-charged IRC 50 (a synthetic carboxyl cation exchanger resin) and from chromaffin granules in vitro which occurred on superfusion of these materials with isotonic NaCl solution (Uvnäs & Aborg 1984a). The initial CA-release, which depending on the intensity of the stimulus amounted to between 0.1 and approximately 5% of the adrenal CA content is suggested to reflect the rapid depletion of a CA pool for immediate release composed of granules 'lined up' for secretion adjacent to the plasma cell membrane. On depolarization of this membrane the granules are assumed to become attached to it and CA release to occur as a cation exchange, between CA+ in the granule matrix and Na+ in the plasma or possibly K+ in the cytoplasm. The transition from depletion to 'steady state' phase is assumed to reflect resynthesis or other compensatory refilling of the releasable depot evoked by its depletion. Cation exchange is suggested to be a general principle in the release of biogenic amines, including transmitter amines and other co-stored charged substances, e.g. polypeptides.