Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists.
Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists.
复制标题
长期暴露于腺苷受体激动剂可抑制肥大细胞腺苷反应性。
DOI：
10.1016/0006-2952(87)90674-5
复制
发表时间：
1987
影响因子：
5.8
通讯作者：
Walker,LL
中科院分区：
文献类型：
--
作者：
Marquardt,DL;Walker,LL
肥大细胞腺苷受体上调功能和数量的慢性暴露于受体拮抗剂，但他们的反应与受体激动剂的长期治疗尚未研究。为了解决这个问题，培养的小鼠骨髓来源的肥大细胞暴露于N-乙基甲酰胺腺苷（NECA），腺苷受体激动剂，增加刺激肥大细胞介质的释放。在1 nM NECA中生长3天的细胞对A23187或抗原释放β-氨基己糖苷酶的反应正常，但外源腺苷增强这种介质释放的能力明显减弱。1 μM NECA暴露10 min后，腺苷反应性部分受到抑制，4 h后完全受到抑制，这种抑制作用可通过洗涤NECA暴露的细胞并将其返回培养4 h以上来逆转。NECA处理的细胞也表现出对腺苷增加细胞环AMP含量的低反应性。这种低反应性是特异性的腺苷受体，外源性异丙肾上腺素能够增加环腺苷酸水平在控制和NECA处理的细胞到类似的程度。因此，慢性NECA暴露诱导肥大细胞腺苷受体的同源脱敏。
Mast cell adenosine receptors are up-regulated functionally and numerically by chronic exposure to receptor antagonists, but their response to long-term treatment with receptor agonists has not been studied. To address this issue cultured mouse bone marrow-derived mast cells were exposed toN-ethylcarboxamide adenosine (NECA), an adenosine receptor agonist that augments stimulated mast cell mediator release. Cells grown for 3 days in 1 nM NECA responded normally to A23187 or antigen in releasing β-hexosaminidase, but the ability of exogenous adenosine to potentiate this mediator release was attenuated markedly. This inhibition of adenosine responsiveness was partially present after 10 min of 1 μM NECA exposure and complete after 4 hr. The inhibitory effects could be reversed by washing NECA-exposed cells and returning them to culture for more than 4 hr. The adenosine present in the fetal calf serum coupled with deoxycoformycin attenuated mast cell adenosine responsiveness. The NECA-treated cells also exhibited a hyporesponsiveness to adenosine's augmentation of cell cyclic AMP content. This hyporesponsiveness was specific for adenosine receptors in that exogenous isoproterenol was able to increase cyclic AMP levels to a similar degree in both control and NECA-treated cells. Thus, chronic NECA exposure induces a homologous desensitization of mast cell adenosine receptors.