Nakaya N, Tasaka K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biochem Pharmacol. 1988 Dec 1;37(23):4523-30. doi: 10.1016/0006-2952(88)90668-5.
When isolated murine myeloblasts and promyelocytes were treated with 3H-histamine (5 x 10(-7) M) in RPMI-1640 medium supplemented with 20% horse serum at 37 degrees, the radioactivity of these cells increased gradually, reaching a maximum after 6 hr. However, when these progenitor cells were pretreated with unlabeled histamine (5 x 10(-7) M) for 1 hr, subsequent exposure to 3H-histamine caused prompt incorporation, the extent of which was more than 3.8 times that seen in cells which were not pretreated. This acceleration was prevented by simultaneous addition of cycloheximide (4 x 10(-7) M) or actinomycin D (10(-7) M) in the pre-incubation stage. While the microsomal fraction of progenitor cells pretreated with histamine initially yielded a higher binding capacity, that of the plasma membrane fraction rose significantly after 1 hr. Most of the incorporated 3H-histamine was detected as unmetabolized. Non-histone chromatin protein had a higher affinity to 3H-histamine than did the DNA fraction of progenitor cell nuclei. Histamine inhibited myeloperoxidase activity of myeloid progenitor cells selectively and dose-dependently without affecting eosinophil peroxidase. These findings suggest that histamine incorporated into murine myeloblasts and promyelocytes induces the synthesis of a specific protein(s) through interaction with the nucleus, and that these proteins, in turn, may be combined into the cell membrane, where they act as a transport system for histamine incorporation.
当将分离的小鼠成髓细胞和早幼粒细胞在补充有20%马血清的RPMI-1640培养基中于37℃用3H-组胺(5×10⁻⁷M)处理时,这些细胞的放射性逐渐增加,6小时后达到最大值。然而,当这些祖细胞用未标记的组胺(5×10⁻⁷M)预处理1小时后,随后暴露于3H-组胺会导致迅速掺入,其掺入程度是未预处理细胞的3.8倍以上。在预孵育阶段同时加入环己酰亚胺(4×10⁻⁷M)或放线菌素D(10⁻⁷M)可阻止这种加速。虽然用组胺预处理的祖细胞的微粒体部分最初具有较高的结合能力,但质膜部分的结合能力在1小时后显著上升。大部分掺入的3H-组胺被检测为未代谢。非组蛋白染色质蛋白对3H-组胺的亲和力高于祖细胞核的DNA部分。组胺选择性地、剂量依赖性地抑制髓系祖细胞的髓过氧化物酶活性,而不影响嗜酸性粒细胞过氧化物酶。这些发现表明,掺入小鼠成髓细胞和早幼粒细胞的组胺通过与细胞核相互作用诱导特定蛋白质的合成,而这些蛋白质反过来可能结合到细胞膜中,在那里它们作为组胺掺入的转运系统发挥作用。