犬の皮膚細切組織による薬物のHistamine遊離に関する定量的研究

With a view to explore and make a comparative study of various drugs as regards their activity in liberating skin histamine a quantitative determination method of in vitro histamine release from chopped dog skin has been devised and a study on the conditions influencing histamine release has been carried out. Abdominal skin was removed from dog and cut in a fixed thickness by a chopper of my own contrivance, consisting of razor blades placed at given spaces and after eliminating the majority of histamine spontaneously diffused out by immersing in Tyrode solution, the skin pieces were shaked in a glass tube containing drug solution to be tested along with a glass bead for one hour at 37°C, and then the histamine content diffusing out in the drug solution and residual histamine in the tissue were determined separately. The histamine releasing activity of drugs depends on the thickness of tissue pieces, temperature, and pH of the solution. In the case of thinner tissue pieces the rate of histamine release either by releaser solution or of spontaneous release proved to be greater. Below 45°C, the rise in temperature enhanced the release by a releaser more markedly than spontaneous release. At 60°C, however, all histamine in tissues diffused out within 60 minutes in the Tyrode solution not containing releaser. In the isotonic buffer solution of pH 6-8 spontaneous release proved to be least, while at the pH either more acidic or basic the rate of release increased. On the alkaline side the effect of releaser of alkaloid salt increased to a greater degree than spontaneous release. This fact suggests that the penetration of alkaloids into the cell wall takes place readily in the form of base. When the tissue is acted upon by the Tyrode solution or by 0.9% saline solution of 78 drugs tested, at 37°C for 60 minutes, these listed in the following released histamine from chopped skin rather markedly: Sinomenine, quinine, quinidine, cinchonine, cinchonidine, optochine, quinoline, ethylmorphine, thebaine, dibucaine, tropacocaine, betaeucaine, sod. cholate, sod. taurocholate, sod. desoxycholate, Irgapyrine, dibenamine, Priscol, jalapa resin, ethylalcohol, acetone. HgCl(2), phenol, thymol, alkylresorcinol, oil of sinapis, oil of chenopodium and ichthammol. On the other hand, salicylic acid, acetylsalicylic acid and cocaine·HCl, under acidic condition, rather suppressed spontaneous release of histamine. The rates of histamine release from dog skin shown by these drugs were found on the whole to be higher than those obtained by Kamimura (Folia pharmacol. japon., 53, 836, 1957) of our laboratory using guinea-pig lung tissues. On the basis of these findings, the significance of histamine release in relation to symptoms of the so-called drug allergy or in the known pharmacological actions of certain drugs were discussed.