Katsuragi T, Tokunaga T, Ohba M, Sato C, Furukawa T
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
Life Sci. 1993;53(11):961-7. doi: 10.1016/0024-3205(93)90449-d.
Effects of isoproterenol and forskolin, which increases intracellular cyclic AMP, on contraction and ATP release in atrial and papillary muscles of guinea pig were evaluated. In the electrically driven-left atrial muscle segments, isoproterenol and forskolin at 0.1 microM produced an ATP release coupled with a positive inotropic effect, the values of net ATP release at 5 min after these drugs being 5.20 +/- 0.59 and 5.37 +/- 0.55 nmoles/g wet weight, respectively. The forskolin evoked-ATP release was unaffected by prazosin plus propranolol or by guanethidine, implying that ATP is released from non-neuronal origin. In contrast, in papillary muscle segments, the test cardiotonics did not elicit any ATP release despite producing contractile response similar to that in atrial preparations. However, there is no difference in ectoATPase activities of both tissues. Adenosine added exogenously inhibited electrically evoked-contraction of the atrium, but not that of the papillary, although inhibitions by verapamil of the contractions were approximately equal in these preparations. These findings suggest that cardiotonics such as isoproterenol produce a liberation of ATP from auricle muscles, but not from ventricle muscles, and that the liberated ATP may mainly be catabolized to adenosine by ectoenzymes and the resultant nucleoside may serve as a functional modulator through stimulation of pre or postsynaptic A1-receptors.
评估了异丙肾上腺素和福斯高林(可增加细胞内环磷酸腺苷)对豚鼠心房和乳头肌收缩及ATP释放的影响。在电驱动的左心房肌段中,0.1微摩尔的异丙肾上腺素和福斯高林产生了与正性肌力作用相关的ATP释放,给药后5分钟时净ATP释放值分别为5.20±0.59和5.37±0.55纳摩尔/克湿重。福斯高林诱发的ATP释放不受哌唑嗪加普萘洛尔或胍乙啶的影响,这表明ATP是从非神经来源释放的。相反,在乳头肌段中,尽管产生了与心房制剂中相似的收缩反应,但受试强心剂并未引起任何ATP释放。然而,两种组织的外切ATP酶活性并无差异。外源性添加的腺苷抑制了心房的电诱发收缩,但不抑制乳头肌的电诱发收缩,尽管维拉帕米对这些制剂中收缩的抑制作用大致相同。这些发现表明,诸如异丙肾上腺素之类的强心剂可使ATP从心房肌而非心室肌中释放出来,并且释放出的ATP可能主要被外切酶分解为腺苷,而产生的核苷可能通过刺激突触前或突触后A1受体而作为一种功能调节剂。