Cyclic nucleotide involvement in histamine release from mast cells--a reevaluation.

Secretory events in cells in general are accompanied by increased levels of cyclic AMP. In mast cells, however, the pattern is reversed. Thus histamine release is associated with a fall in cAMP. It has been suggested that the lowered levels of cAMP lead to an increase in membrane permeability towards calcium and that an influx of such ions triggers the release mechanisms. It has further been reported that high levels of cAMP inhibit histamine release by decreasing the permeability. However, evidence has now accumulated indicating that this general concept is far too simplistic. Studies are reviewed which imply that there is little or no correlation between histamine release and intracellular levels of cyclic nucleotides. A new working hypothesis with respect to the role of these nucleotides in mast cell secretion is proposed.