腺苷的抗肾上腺素能作用及其被百日咳毒素的阻断：在从豚鼠、大鼠和衰竭的人类心脏分离出的心肌细胞中的比较研究。

The anti-adrenergic effect of adenosine and its blockade by pertussis toxin: a comparative study in myocytes isolated from guinea-pig, rat and failing human hearts.

作者信息

Brown L A, Humphrey S M, Harding S E

机构信息

Department of Cardiac Medicine, National Heart & Lung Institute, London.

出版信息

Br J Pharmacol. 1990 Oct;101(2):484-8. doi: 10.1111/j.1476-5381.1990.tb12734.x.

DOI:10.1111/j.1476-5381.1990.tb12734.x

PMID:1979512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917684/

Abstract

In intact ventricular preparation, adenosine has been shown to reduce the beta-adrenoceptor-induced increase in contraction (the anti-adrenergic effect). In the present study we have investigated this effect of adenosine on isolated ventricular myocytes from failing human heart and normal guinea-pig and rat heart. 2. Adenosine in the absence of beta-adrenoceptor-mediated stimulation had no effect on contraction in human and guinea-pig myocytes but produced a variable effect in rat myocytes. 3. 8-Cyclopentyl 1,3-dipropylxanthine (CPX), a selective A1-receptor antagonist, antagonised the anti-adrenergic effect of adenosine in guinea-pig myocytes. 4. The anti-adrenergic effect of adenosine was greater in guinea-pig than rat myocytes and even more pronounced in cells isolated from failing human heart. 5. Pertussis toxin-pretreatment at 35 degrees C of guinea-pig and human myocytes abolished the anti-adrenergic effect of adenosine. Longer exposure to higher concentrations of pertussis toxin was required for complete abolition in human compared to guinea-pig cells. 6. These results support the suggestion that the adenosine receptors mediating the anti-adrenergic effect of adenosine are of the A1 subtype and are coupled to the inhibitory guanine nucleotide binding protein, Gi/Go. 7. Pertussis toxin pretreatment increased the sensitivity of guinea-pig myocytes to isoprenaline in the absence of adenosine; the EC50 value was decreased by a factor of 10. This suggests that Gi may exert a tonic inhibitory effect on the beta-adrenoceptor/adenylate cyclase interaction in normal myocardium.

摘要

在完整心室标本中，腺苷已被证明可降低β肾上腺素能受体诱导的收缩增强（抗肾上腺素能效应）。在本研究中，我们研究了腺苷对来自衰竭人心脏以及正常豚鼠和大鼠心脏的离体心室肌细胞的这种效应。2. 在不存在β肾上腺素能受体介导的刺激时，腺苷对人及豚鼠肌细胞的收缩无影响，但对大鼠肌细胞产生可变效应。3. 8-环戊基-1,3-二丙基黄嘌呤（CPX），一种选择性A1受体拮抗剂，可拮抗腺苷对豚鼠肌细胞的抗肾上腺素能效应。4. 腺苷对豚鼠肌细胞的抗肾上腺素能效应大于对大鼠肌细胞的效应，在从衰竭人心脏分离的细胞中更明显。5. 在35℃对豚鼠和人肌细胞进行百日咳毒素预处理可消除腺苷的抗肾上腺素能效应。与豚鼠细胞相比，人细胞需要更长时间暴露于更高浓度的百日咳毒素才能完全消除该效应。6. 这些结果支持以下观点：介导腺苷抗肾上腺素能效应的腺苷受体为A1亚型，并与抑制性鸟嘌呤核苷酸结合蛋白Gi/Go偶联。7. 百日咳毒素预处理增加了豚鼠肌细胞在无腺苷时对异丙肾上腺素的敏感性；EC50值降低了10倍。这表明Gi可能对正常心肌中的β肾上腺素能受体/腺苷酸环化酶相互作用发挥紧张性抑制作用。