Akbar M, Okajima F, Tomura H, Shimegi S, Kondo Y
Department of Physical Biochemistry, Gunma University, Maebashi, Japan.
Mol Pharmacol. 1994 May;45(5):1036-42.
Chinese hamster ovary cells were transfected with both A1 adenosine receptor and muscarinic type 3 acetylcholine receptor cDNAs. The muscarinic receptor agonist carbachol stimulated phospholipase C activity, resulting in Ca2+ mobilization and arachidonate release. N6-Cyclopentyladenosine (CPA), an A1 receptor agonist, did not activate Ca(2+)-related signal transduction systems by itself but instead inhibited cAMP accumulation. In the presence of carbachol, however, the A1 receptor agonist enhanced muscarinic receptor agonist-induced phospholipase C/Ca2+ responses. In addition, the arachidonate release caused by Ca2+ ionophores or thapsigargin was also amplified by CPA, without a change in phospholipase C activity. Thus, CPA augments Ca(2+)-mediated phospholipase A2 activation in addition to and separate from its ability to amplify phospholipase C-mediated Ca2+ mobilization. Because the permissive actions of CPA on phospholipase C and phospholipase A2 activation were each reversed by pertussis toxin treatment, in a manner similar to that of the CPA-induced inhibition of cAMP accumulation, we conclude that a single species of A1 receptor expressed in Chinese hamster ovary cells can couple to multiple signal transduction systems stemming from phospholipase C stimulation, phospholipase A2-mediated and Ca(2+)-dependent arachidonate release, and inhibition of cAMP accumulation. A pertussis toxin-sensitive G protein (or proteins) mediates the permissive actions of the A1 receptor in the stimulation of phospholipase C- and phospholipase A2-mediated arachidonate release.
将A1腺苷受体和毒蕈碱型3乙酰胆碱受体的互补DNA转染到中国仓鼠卵巢细胞中。毒蕈碱受体激动剂卡巴胆碱刺激磷脂酶C活性，导致钙离子动员和花生四烯酸释放。A1受体激动剂N6-环戊基腺苷（CPA）本身并不激活与钙离子相关的信号转导系统，而是抑制环磷酸腺苷（cAMP）的积累。然而，在卡巴胆碱存在的情况下，A1受体激动剂增强了毒蕈碱受体激动剂诱导的磷脂酶C/钙离子反应。此外，钙离子载体或毒胡萝卜素引起的花生四烯酸释放也被CPA放大，而磷脂酶C活性没有变化。因此，CPA除了增强磷脂酶C介导的钙离子动员外，还增强了钙离子介导的磷脂酶A2激活，且这两种作用相互独立。由于CPA对磷脂酶C和磷脂酶A2激活的允许作用都被百日咳毒素处理所逆转，其方式类似于CPA诱导的对cAMP积累的抑制作用，我们得出结论，在中国仓鼠卵巢细胞中表达的单一类型的A1受体可以与源自磷脂酶C刺激、磷脂酶A2介导和钙离子依赖性花生四烯酸释放以及cAMP积累抑制的多种信号转导系统偶联。一种对百日咳毒素敏感的G蛋白介导A1受体在刺激磷脂酶C和磷脂酶A2介导的花生四烯酸释放中的允许作用。
