In vitro histamine release from intracellular large granules of the dog liver was determined and compared with that from the chopped tissue. The histamine release from the large granules depended on the concentration, duration of action, temperature and pH of histamine liberators. Histamine was released by all the liberators tested even at 0°C less than at 37°C. The action of basic liberators such as sinomenine increased with increasing alkalinity of medium.
Dibucaine hydrochloride, decylamine hydrochloride, HgCl(2), quinine hydrochloride and tutocaine hydrochloride at pH 7-8 and 6mM concentration released over 50 per cent of histamine from the large granules. Under the same conditions ethylmorphine hydrochloride, toluidine blue, procaine hydrochloride, saponin (0.1 per cent), tropacocaine hydrochloride, sodium cholate, Compound 48/80 (0.1 per cent), sinomenine hydrochloride, Tween 20 (0.2 per cent), cocaine hydrochloride and xylocaine hydrochloride revealed the histamine liberating action in the descending order named. Histamine release from the granules by these substances was larger in variable degrees as compared with that from the chopped tissue. Sodium salicylate inhibited the release from the granules and chopped liver by other substances, while diphenhydamine and guaiazulen did not reveal such an inhibitory action but rather accelerated the release though slightly. The histamine release from the chopped tissue by sinomenine and decylamine was inhibited by uranil nitrate, but it was not the same from the large granules. The lack of oxygen accelerated the histamine release by decylamine from both the granules and chopped tissues, but did not reveal any significant effect on the action of other liberators. In in vitro anaphylaxis histamine release occurred in the chopped tissue but not in the granules. As far as basic liberators are concerned, there seemed to be some correlation between the histamine release ability and the heparin combining power. However, the surface activity or the hemolytic power of liberators and the histamine release ability was not to be necessarily in parallel with each other in degree. Interpreting the intracellular large granules as the granules of mast cells and in the light of the above findings the author discussed the respective mode of action of the liberators on mast cells and on their granules.