Histamine release from mast cell granules

Rat peritoneal mast cells were separated from other cells by differential centrifugation in concentrated serum albumin. Granules were isolated form these cells by ultrasonic disintegration and subsequent centrifugation. 60-80% of the granules had intact membranes and retained their histamine store in a physiological salt solution. Histamine was released from the granules with intact membranes by Ca2+, 10 mM, in the presence of phosphatidyl serine, 25--50 microgram/ml. The release was initiated in 15 sec and completed in 16 min. Other divalent cations in 10 mM concentration, viz. Mg2+, Ba2+, Sr2+, Ni2+ and Mn2+, also released histamine from the granules in the presence of phosphatidyl serine. When histamine release was induced by calcium and phosphatidyl serine the calcium uptake in the granules was remarkably increased. Ca2+ could thus displace histamine from the granule matrix. The possibility that calcium with phosphatidyl serine may change the granule membrane permeability is discussed.