Gustafsson L, Fredholm B B, Hedqvist P
Acta Physiol Scand. 1981 Mar;111(3):269-80. doi: 10.1111/j.1748-1716.1981.tb06736.x.
The ability of theophylline and other phosphodiesterase inhibitors to alter contractile responses to cholinergic nerve stimulation was investigated in isolated longitudinal muscle of the guinea pig ileum. Theophylline in low concentrations (10-100 microM), having no or little effect on measured phosphodiesterase activity, antagonized inhibitory effects of exogenous adenosine. In higher concentrations (0.1-10 mM), shown to be effective in inhibiting phosphodiesterase, theophylline as well as a "pure" cAMP phosphodiesterase inhibitor, ZK 62, 711, inhibited contractile responses. Dipyridamole and dilazep, inhibitors of adenosine inactivation, and also selective inhibitors of cAMP and cGMP phosphodiesterase, respectively, were found to enhance effects of exogenous adenosine and to cause a marked leftward shift to adenosine threshold dose. When dipyridamole and dilazep by themselves had inhibitory effects these could be antagonized by theophylline, suggesting an action through increased levels of endogenous adenosine. As a further indication of endogenous adenosine modulating neurotransmission low concentrations of theophylline enhanced responses to transmural stimulation. Endogenous purine concentrations in tissues and bath media were measured by HPLC. Because of tissue and microbial adenosine inactivation direct estimates of extracellular adenosine concentration could not be obtained. However, adenosine levels increased during transmural stimulation, and during inhibition of adenosine inactivation were sufficient, even in the bath medium, to interfere with the cholinergic neurotransmission.
在豚鼠回肠的离体纵行肌中，研究了茶碱及其他磷酸二酯酶抑制剂改变对胆碱能神经刺激的收缩反应的能力。低浓度（10 - 100微摩尔）的茶碱对测得的磷酸二酯酶活性无影响或影响很小，可拮抗外源性腺苷的抑制作用。在较高浓度（0.1 - 10毫摩尔）时，已证明茶碱可有效抑制磷酸二酯酶，它以及一种“纯”的环磷酸腺苷（cAMP）磷酸二酯酶抑制剂ZK 62,711可抑制收缩反应。双嘧达莫和地拉齐普分别是腺苷失活抑制剂以及cAMP和环磷酸鸟苷（cGMP）磷酸二酯酶的选择性抑制剂，它们被发现可增强外源性腺苷的作用，并使腺苷阈值剂量显著左移。当双嘧达莫和地拉齐普自身具有抑制作用时，这些作用可被茶碱拮抗，提示其作用是通过内源性腺苷水平的升高。作为内源性腺苷调节神经传递的进一步证据，低浓度的茶碱可增强对透壁刺激的反应。通过高效液相色谱法（HPLC）测量组织和浴液介质中的内源性嘌呤浓度。由于组织和微生物对腺苷的失活作用，无法直接获得细胞外腺苷浓度的估计值。然而，在透壁刺激期间腺苷水平升高，并且在抑制腺苷失活期间，即使在浴液介质中，腺苷水平也足以干扰胆碱能神经传递。
