腺苷通过A(2B)腺苷受体诱导豚鼠气管上皮细胞中环状AMP的形成并抑制内皮素-1的产生/分泌。
Adenosine induces cyclic-AMP formation and inhibits endothelin-1 production/secretion in guinea-pig tracheal epithelial cells through A(2B) adenosine receptors.
作者信息
Pelletier S, Dubé J, Villeneuve A, Gobeil F, Bernier S G, Battistini B, Guillemette G, Sirois P
机构信息
Institut de Pharmacologie de Sherbrooke, Faculté de Médecine, Université de Sherbrooke, Sherbrooke (PQ) Canada.
出版信息
Br J Pharmacol. 2000 Jan;129(2):243-50. doi: 10.1038/sj.bjp.0702999.
Abstract
- The adenosine receptor subtype mediating adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation and the effect of its activation on endothelin-1 (ET-1) secretion were studied in primary cultures of tracheal epithelial cells. 2. Adenosine analogues showed the following rank order of potency (pD(2) value) and intrinsic activity on the generation of cyclic AMP by tracheal epithelial cells: 5'-N-ethylcarboxyamidoadenosine (NECA, A(1)/A(2A)/A(2B), pD(2): 5.44+/-0.16)>adenosine (ADO, non selective, pD(2): 4.99+/-0. 09; 71+/-9% of NECA response) >/=2-Cl-adenosine (2CADO, non selective, pD(2): 4.72+/-0.14; 65+/-9% of NECA response)>>>CGS21680 (A(2A); inactive at up to 100 microM). 3. Cyclic AMP formation stimulated by NECA in guinea-pig tracheal epithelial cells was inhibited by adenosine receptor antagonist with the following order of apparent affinity (pA(2) value): Xanthine amine congeners (XAC, A(2A)/A(2B), 7.89+/-0.22)>CGS15943 (A(2A)/A(2B), 7.24+/-0. 26)>ZM241385 (A(2A), 6.69+/-0.14)>DPCPX (A(1), 6.51+/-0. 14)>3n-propylxanthine (weak A(2B), 4.30+/-0.10). This rank order of potency is typical for A(2B)-adenosine receptor. 4. Adenosine decreased basal and LPS-stimulated irET production in a concentration-dependent manner. Moreover, NECA but not CGS21680 inhibited LPS-induced irET production. 5. The inhibitory effect of NECA on LPS-induced irET production was reversed by XAC (pA(2)=8.84+/-0. 12) and DPCPX (pA(2)=8.10+/-0.22). 6. These results suggested that adenosine increased cyclic AMP formation and inhibited irET production/secretion by guinea-pig tracheal epithelial cells through the activation of a functional adenosine receptor that is most likely the A(2B) subtype. This adenosine receptor may be involved in the regulation of the level of ET-1 production/secretion by guinea-pig tracheal epithelial cells in physiological as well as in pathophysiological conditions.
摘要
- 在气管上皮细胞原代培养物中，研究了介导3':5'-环磷酸腺苷（环磷腺苷）形成的腺苷受体亚型及其激活对内皮素-1（ET-1）分泌的影响。2. 腺苷类似物在气管上皮细胞产生环磷腺苷方面表现出以下效价顺序（pD(2)值）和内在活性：5'-N-乙基羧酰胺腺苷（NECA，A(1)/A(2A)/A(2B)，pD(2)：5.44±0.16）>腺苷（ADO，非选择性，pD(2)：4.99±0.09；NECA反应的71±9%）≥2-氯腺苷（2CADO，非选择性，pD(2)：4.72±0.14；NECA反应的65±9%）>>>CGS21680（A(2A)；在高达100μM时无活性）。3. 豚鼠气管上皮细胞中NECA刺激的环磷腺苷形成被腺苷受体拮抗剂抑制，其表观亲和力顺序（pA(2)值）如下：黄嘌呤胺类似物（XAC，A(2A)/A(2B)，7.89±0.22）>CGS15943（A(2A)/A(2B)，7.24±0.26）>ZM241385（A(2A)，6.69±0.14）>DPCPX（A(1)，6.51±0.14）>3-丙基黄嘌呤（弱A(2B)，4.30±0.10）。这种效价顺序是A(2B)型腺苷受体的典型特征。4. 腺苷以浓度依赖的方式降低基础和脂多糖刺激的免疫反应性ET产生。此外，NECA而非CGS21680抑制脂多糖诱导的免疫反应性ET产生。5. NECA对脂多糖诱导的免疫反应性ET产生的抑制作用被XAC（pA(2)=8.84±0.12）和DPCPX（pA(2)=8.10±0.22）逆转。6. 这些结果表明，腺苷通过激活一种功能性腺苷受体增加环磷腺苷形成并抑制豚鼠气管上皮细胞免疫反应性ET的产生/分泌，该受体很可能是A(2B)亚型。这种腺苷受体可能参与豚鼠气管上皮细胞在生理和病理生理条件下ET-1产生/分泌水平的调节。
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