Inhibition of Histamine Release by Histamine controlled by H2 Receptor
Inhibition of Histamine Release by Histamine controlled by H2 Receptor
复制标题
H2 受体控制组胺抑制组胺释放
作者：
L. M. Lichtenstein;E. Gillespie
增加人白细胞制剂中3‘-5’-单磷酸腺苷(CAMP)水平的药物，如儿茶酚胺、甲基黄嘌呤和前列腺素，抑制抗原诱导的、IgE抗体介导的从人白细胞(嗜碱性粒细胞)1-3释放组胺。不仅增加cAMP水平和抑制组胺释放的剂量-反应关系相似，而且这两个事件的动力学也是平行的，并被认为是一个工作假说，即人嗜碱性粒细胞(和肥大细胞)的cAMP水平的变化调节体外过敏反应4-6。我们发现外源性组胺可以增加人白细胞制剂中cAMP的水平，并阻止内源性组胺的释放。这发生在组胺浓度(约10−6M)时，组胺存在于所研究的细胞悬浮液中。出于这个原因，我们认为组胺可以通过降低其他靶细胞(组织肥大细胞、嗜碱性粒细胞)对致敏挑战的反应来“反馈”控制过敏反应的传播。未观察到抗组胺药物对组胺释放的明显抑制作用：几种抗组胺药物在10−3 M至10−4 M的浓度下几乎没有作用，较高浓度的这些药物要么自身抑制组胺释放，要么具有细胞毒性2，7。
AGENTS which increase the intracellular level of adenosine 3′-5′-monophosphate (cyclic AMP) in human leukocyte preparations such as the catecholamines, methylxanthines and prostaglandins, inhibit the antigen induced, IgE antibody mediated release of histamine from human leukocytes (basophils)1–3. Not only are the dose response relationships for increased cyclic AMP levels and the inhibition of histamine release similar, but the kinetics of the two events are also parallel and it is accepted as a working hypothesis that changes in the cyclic AMP level of human basophils (and mast cells) modulate the in vitro allergic response4–6. Recently, we showed that exogenous histamine could increase the cyclic AMP level of human leukocyte preparations and stop the release of endogenous histamine. This occurred at concentrations of histamine (about 10−6 M) which are present in the cell suspension under study7. For this reason we suggested that histamine could “feedback” to control the spread of an allergic response by decreasing the response of other target cells (tissue mast cells, blood basophils) to an allergenic challenge. No clear effect of antihistamines on the inhibition of histamine release by histamine was observed: concentrations up to 10−3 M to 10−4 M of several antihistamines had little effect and higher concentrations of these drugs either caused inhibition of histamine release themselves or were cytotoxic2,7.