Welford L A, Cusack N J, Hourani S M
Department of Pharmacology, University of London, King's College, Strand.
Eur J Pharmacol. 1987 Sep 2;141(1):123-30. doi: 10.1016/0014-2999(87)90418-3.
The dephosphorylation of adenine nucleotides and their analogues by ectonucleotidases on the guinea-pig urinary bladder was studied using HPLC. The rate of dephosphorylation of each analogue was compared with its pharmacological potency at causing contraction. ATP, ADP and AMP were rapidly dephosphorylated, and substitution on the purine ring did not affect the rate of breakdown. The ectonucleotidases showed stereoselectivity towards the ribose moiety and towards the polyphosphate chain. In general, methylene isosteres of the nucleotides, and analogues in which one of the oxygen atoms on the terminal phosphate had been replaced, were resistant to degradation. None of the analogues that were readily dephosphorylated are more potent than ATP, and most but not all of the analogues resistant to degradation are more potent than ATP, suggesting that while resistance to degradation does not in itself confer high potency, susceptibility to degradation does limit the potency of ATP and its degradable analogues.
利用高效液相色谱法研究了豚鼠膀胱上的外核苷酸酶对腺嘌呤核苷酸及其类似物的去磷酸化作用。将每种类似物的去磷酸化速率与其引起收缩的药理活性进行了比较。ATP、ADP和AMP迅速去磷酸化，嘌呤环上的取代不影响分解速率。外核苷酸酶对核糖部分和多磷酸链表现出立体选择性。一般来说，核苷酸的亚甲基电子等排体以及末端磷酸上的一个氧原子被取代的类似物对降解具有抗性。所有易于去磷酸化的类似物都不比ATP更具活性，大多数（但不是全部）抗降解的类似物比ATP更具活性，这表明虽然抗降解本身并不赋予高效性，但易降解确实限制了ATP及其可降解类似物的活性。
