Histamineとその類似化合物のモルモット顎下腺に対するcyclic AMP増加作用

モルモット顎下腺切片のcyclic AMP含量に及ぼすhistamineとその類似化合物の効果,およびこの効果に対するhistamine拮抗薬ならびにhistamine代謝酵素阻害薬の影響をしらべ,次の成績を得た.1) 被検のhistamine受容体活性薬はcyclic AMPレベルを用量依存的に上昇させた.histamineと4-methylhistamineのED(50)値はそれぞれ約1.3×10(-5)Mおよび2.2×10(-5)Mであった.4-methylhistamineの最大効果はhistamineのそれを上回った.2) 2-(2-pyridyl)ethylamineはhistamineや4-methylhistamineと比較して,効果がはるかに劣っていた.3) metiamideはhistamineおよび4-methylhistamineによるcyclic AMPレベルの上昇を著しく抑制した.しかし, mepyramineは無効であった.4) aminoguanidineとquinacrineの併用は, histamineのcyclic AMPレベル上昇効果に対して影響を及ぼさなかった.以上の成績は,モルモット顎下腺には, cyclic AMP増加を媒介するH(2)型のhistamine受容体が存在することを示唆する.

The effects of histamine and its analogues on the cyclic AMP levels in the submandibular glands of guinea pigs and the characteristics of the receptors which mediate such effects were investigated. Histamine and 4-methylhistamine dose-dependently increased the cyclic AMP levels in chopped submandibular glands. The ED(50) values for histamine and 4-methylhistamine were approximately 1.3×10(-5)M and 2.2×10(-5)M, respectively. 4-Methylhistamine had a higher efficacy than histamine. 2-(2-Pyridyl)ethylamine was far less effective than either histamine or 4-methylhistamine. Although metiamide markedly inhibited the cyclic AMP-increasing effects of histamine and 4-methylhistamine, mepyramine was completely ineffective. A combination of aminoguanidine and quinacrine had no influence on the effect of histamine on the cyclic AMP levels. From these results it was concluded that histamine H(2)-receptors which mediate the cyclic AMP increase are present in the guinea-pig submandibular gland.