Jónsson O, Halldórsson H, Kjeld M, Thorgeirsson G
Department of Pharmacology, University of Iceland, Reykjavík.
Biochim Biophys Acta. 1998 Jan 8;1379(1):143-50. doi: 10.1016/s0304-4165(97)00091-3.
Meta-iodo-benzylguanidine (MIBG), a selective inhibitor of mono-ADP-ribosylation, has been shown to inhibit histamine induced inositol-trisphosphate and prostacyclin production. The purpose of this study was to evaluate the effect of MIBG on the binding of histamine to the H1-receptor and to study its effects on phospholipid metabolism in human endothelial cells. The effects of MIBG and MIBA (meta-iodo-benzylamine), which does not affect cellular ADP-ribosylation, on agonist induced cGMP production in cultured HUVEC's were measured by RIA and a binding study carried out to evaluate their effects on the binding of [3H]mepyramine to membrane fractions. MIBG (0.3 mM) reduced histamine induced cGMP production by 90.8% but did not inhibit the cGMP production induced by other agonists. MIBA had no effect. MIBG also reduced the binding of [3H]mepyramine (1.0 nM) to membrane fractions with IC50 at 0.094 mM and maximal inhibition (83%) at 0.22mM MIBG. The calculated Ki was 0.076mM. MIBG and MIBA altered phospholipid metabolism in a similar way as the cationic amphiphilic drug propranolol. MIBA caused up to 42% reduction in [3H]mepyramine binding, probably due to its inhibition of nonspecific binding. These results indicate that MIBG reduces histamine induced cGMP production by inhibiting its binding to H1-receptors and alters phospholipid metabolism in cultured endothelial cells in a similar way as known cationic amphiphilic drugs.
间碘苄胍（MIBG）是一种单磷酸腺苷核糖基化的选择性抑制剂，已被证明可抑制组胺诱导的肌醇三磷酸和前列环素的产生。本研究的目的是评估MIBG对组胺与H1受体结合的影响，并研究其对人内皮细胞磷脂代谢的作用。通过放射免疫分析法（RIA）测定了MIBG和不影响细胞ADP核糖基化的间碘苄胺（MIBA）对培养的人脐静脉内皮细胞（HUVEC）中激动剂诱导的环鸟苷酸（cGMP）产生的影响，并进行了一项结合研究以评估它们对[3H]美吡拉敏与膜组分结合的影响。MIBG（0.3 mM）使组胺诱导的cGMP产生减少了90.8%，但不抑制其他激动剂诱导的cGMP产生。MIBA没有作用。MIBG还降低了[3H]美吡拉敏（1.0 nM）与膜组分的结合，IC50为0.094 mM，在0.22 mM MIBG时最大抑制率为83%。计算得出的Ki为0.076 mM。MIBG和MIBA对磷脂代谢的影响与阳离子两亲性药物普萘洛尔相似。MIBA使[3H]美吡拉敏结合最多减少42%，可能是由于其对非特异性结合的抑制作用。这些结果表明，MIBG通过抑制组胺与H1受体的结合来减少组胺诱导的cGMP产生，并以与已知阳离子两亲性药物相似的方式改变培养的内皮细胞中的磷脂代谢。
