Katsuragi T, Furuta K, Harada T, Furukawa T
Clin Exp Pharmacol Physiol. 1985 Jan-Feb;12(1):73-8. doi: 10.1111/j.1440-1681.1985.tb00305.x.
The effects of ATP, adenosine and N6-substituted adenosines, adenosine receptor agonists, on the twitch contraction of guinea-pig ileum evoked by transmural stimulation were evaluated. Adenosine and ATP produced an immediate and concentration dependent inhibition of the twitch, IC50 being 1.1 X 10(-5) mol/l and 1.2 X 10(-5) mol/l, respectively. N6-l-phenylisopropyl adenosine (L-PIA), N6-cyclohexyl adenosine (CHA) and N6-allyl adenosine also induced inhibitions which were gradual and persistent, IC50 being 2.6 X 10(-8), 2.7 X 10(-8) and 5.4 X 10(-7) mol/l, respectively. Dipyridamole (10(-7) mol/l), an adenosine uptake inhibitor, markedly augmented the inhibition evoked by adenosine and ATP, but not that by three N6-substituted adenosines, while theophylline (10(-4) mol/l) almost completely antagonized the inhibitory effects of all purine compounds. IC50 value of adenosine in the presence of dipyridamole (5 X 10(-7) mol/l) was shifted to the left about 50 times from the control, whereas that of L-PIA was virtually unchanged. Tissue-medium ratios indicating uptake of [3H]adenosine, [3H]ATP and [3H]CHA into the segment were 3.23 (s.e.m. = 0.59), 3.59 (s.e.m. = 0.78) and 0.41 (s.e.m. = 0.04), respectively. These results suggest that not only adenosine and ATP but also these N6-substituted adenosines are potent agonists for the P1 receptor, implying a similarity between P1 and A1 receptor in a functional role and these purine compounds may thereby modulate cholinergic neurotransmission by altering adenylate cyclase activity.
评估了ATP、腺苷及N6-取代腺苷（腺苷受体激动剂）对经壁刺激诱发的豚鼠回肠抽搐收缩的影响。腺苷和ATP对抽搐产生即时且浓度依赖性的抑制作用，IC50分别为1.1×10⁻⁵mol/L和1.2×10⁻⁵mol/L。N6-1-苯基异丙基腺苷（L-PIA）、N6-环己基腺苷（CHA）和N6-烯丙基腺苷也诱导出逐渐且持久的抑制作用，IC50分别为2.6×10⁻⁸、2.7×10⁻⁸和5.4×10⁻⁷mol/L。腺苷摄取抑制剂双嘧达莫（10⁻⁷mol/L）显著增强了腺苷和ATP诱发的抑制作用，但对三种N6-取代腺苷诱发的抑制作用无增强效果，而茶碱（10⁻⁴mol/L）几乎完全拮抗了所有嘌呤化合物的抑制作用。在双嘧达莫（5×10⁻⁷mol/L）存在的情况下，腺苷的IC50值相对于对照组向左移动了约50倍，而L-PIA的IC50值实际上未变。表明[³H]腺苷、[³H]ATP和[³H]CHA进入肠段的组织-培养基比率分别为3.23（标准误=0.59）、3.59（标准误=0.78）和0.41（标准误=0.04）。这些结果表明，不仅腺苷和ATP，而且这些N6-取代腺苷都是P1受体的强效激动剂，这意味着P1和A1受体在功能作用上具有相似性，这些嘌呤化合物可能通过改变腺苷酸环化酶活性来调节胆碱能神经传递。
