ADENOSINE A(2B) RECEPTORS EVOKE INTERLEUKIN-8 SECRETION IN HUMAN MAST-CELLS - AN ENPROFYLLINE-SENSITIVE MECHANISM WITH IMPLICATIONS FOR ASTHMA
ADENOSINE A(2B) RECEPTORS EVOKE INTERLEUKIN-8 SECRETION IN HUMAN MAST-CELLS - AN ENPROFYLLINE-SENSITIVE MECHANISM WITH IMPLICATIONS FOR ASTHMA
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DOI：
10.1172/jci118245
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发表时间：
1995-10-01
影响因子：
15.9
通讯作者：
BIAGGIONI, I
中科院分区：
文献类型：
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作者：
FEOKTISTOV, I;BIAGGIONI, I
腺苷增强肥大细胞的激活，但受体类型和分子机制尚未明确。因此，我们研究了腺苷对人肥大细胞系HMC-1的影响。A（2a）选择性激动剂CGS21680和A(2a)/A（2b）非选择性激动剂5' n -乙基羧胺腺苷（NECA）均可增加cAMP，但NECA的有效性是NECA的四倍，Hill系数为0.55，表明A（2a）和A（2b）受体的存在，NECA 10 μ M可诱导HMC-1释放IL-8，但CGS21680 10 μ M没有作用。在单独的研究中，我们发现enprofylline，一种以前被认为缺乏腺苷拮抗特性的平哮喘药，作为A（2b）受体拮抗剂，茶碱和enprofylline 300 μ M均能完全阻断NECA、NECA对IL-8的释放，而CGS21680则不能，通过霍乱和百日咳毒素不敏感机制增加肌醇磷酸形成和细胞内钙动员。综上所述，A（2a）和A（2b）受体均存在于hcc -1细胞中，并与腺苷酸环化酶偶联。此外，A（2b）受体与磷脂酶C偶联并引起IL-8的释放，这一作用被茶碱和enprofylline阻断，这一机制可能有助于它们的平喘作用。
Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A(2a) selective agonist CGS21680 and the A(2a)/A(2b) nonselective agonist 5'N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A(2a) and A(2b) receptors, NECA 10 mu M evoked IL-8 release from HMC-1, but CGS21680 10 mu M had no effect, In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of A(2b) receptors at concentrations achieved clinically, Both theophylline and enprofylline 300 mu M completely blocked the release of IL-8 by NECA, NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism, In conclusion, both A(2a) and A(2b) receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, A(2b) receptors are coupled to phospholipase C and evoke IL-8 release, This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects.