The molecular mechanism of nondegranulative release of biogenic amines.

According to current teaching biogenic amines are released by exocytosis, i.e. by evacuation of amine storing vesicles or granules into the extracellular space. The release of transmitter amines is quantal, i.e. occurs in packs of transmitter molecules. These packs are assumed to be identical with vesicle contents, in other words, the smallest releasable quantum equals the amine content of one vesicle. However, there are experimental observations which do not fit in with this version of an exocytotic release theory. Observed quantitative discrepancies could be explained if the release mechanism allowed a fractional release of transmitter amine from several vesicles instead of the total evacuation of a few. The lack of adequate knowledge about the mechanisms of storage of biogenic amines within the vesicles has up til now rendered it difficult to envisage the machinery behind a fractional release of the amine content of a vesicle. In extensive in-vitro studies we have found that the matrices of amine storing granules (i.e. from mast cells, chromaffin cells and nerve terminals) show the properties of weak cation exchanger materials, carboxyl groups serving as amine binding ionic sites. When exposed to cations like sodium and potassium ions, the amines are released from their storage sites according to kinetics characteristic of weak cation exchangers. In vivo, amine release from cat adrenals on splanchnic nerve stimulation also occurs according to ion exchange kinetics. Histamine release from mast cells is considered to occur as the result of degranulation, i.e. the expulsion of histamine storing granules to the extracellular space, a typical example of exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)