In corpus cavernosum (CC), guanosine triphosphate (GTP) is converted into cyclic guanosine monophosphate (cGMP) to induce erection. The action of cGMP is terminated by phosphodiesterases and efflux transporters, which pump cGMP out of the cell. The nucleotides, GTP, and cGMP were detected in the extracellular space, and their hydrolysis lead to the formation of intermediate products, among them guanosine. Therefore, our study aims to pharmacologically characterize the effect of guanosine in isolated CC from mice. The penis was isolated and functional and biochemical analyses were carried out. The guanine-based nucleotides GTP, guanosine diphosphate, guanosine monophosphate, and cGMP relaxed mice corpus cavernosum, but the relaxation (90.7 ± 12.5%) induced by guanosine (0.000001–1 mM) was greater than that of the nucleotides (~ 45%, P < 0.05). Guanosine-induced relaxation was not altered in the presence of adenosine type 2A and 2B receptor antagonists. No augment was observed in the intracellular levels of cyclic adenosine monophosphate in tissues stimulated with guanosine. Inhibitors of nitric oxide synthase (L-NAME, 100 μM) and soluble guanylate cyclase (ODQ, 10 μM) produced a significant reduction in guanosine-induced relaxation in all concentrations studied, while in the presence of tadalafil (300 nM), a significant increase was observed. Pre-incubation of guanosine (100 μM) produced a 6.6-leftward shift in tadalafil-induced relaxation. The intracellular levels of cGMP were greater when CC was stimulated with guanosine. Inhibitors of ecto-nucleotidases and xanthine oxidase did not interfere in the response induced by guanosine. In conclusion, our study shows that guanosine relaxes mice CC and opens the possibility to test its role in models of erectile dysfunction.

中文翻译：

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鸟苷是一种基于鸟嘌呤的核苷，可通过 cGMP 积累松弛小鼠的分离的海绵体。

在阴茎海绵体 (CC) 中，三磷酸鸟苷 (GTP) 转化为环磷酸鸟苷 (cGMP) 以诱导勃起。cGMP 的作用被磷酸二酯酶和外排转运蛋白终止，它们将 cGMP 泵出细胞。在细胞外空间检测到核苷酸、GTP 和 cGMP，它们的水解导致中间产物的形成，其中包括鸟苷。因此，我们的研究旨在从药理学上表征鸟苷在小鼠分离的 CC 中的作用。分离阴茎并进行功能和生化分析。基于鸟嘌呤的核苷酸 GTP、二磷酸鸟苷、一磷酸鸟苷和 cGMP 使小鼠海绵体松弛，但鸟苷 (0.000001–1 mM) 诱导的松弛 (90.7 ± 12.5%) 大于核苷酸 (~ 45%,磷 < 0.05)。在腺苷 2A 和 2B 型受体拮抗剂存在的情况下，鸟苷诱导的松弛没有改变。在用鸟苷刺激的组织中，没有观察到环磷酸腺苷的细胞内水平增加。一氧化氮合酶 (L-NAME, 100 μM) 和可溶性鸟苷酸环化酶 (ODQ, 10 μM) 的抑制剂在所有研究浓度下都显着降低了鸟苷诱导的松弛，而在他达拉非 (300 nM) 存在下，观察到增加。鸟苷 (100 μM) 的预孵育在他达拉非诱导的松弛中产生了 6.6 的左移。当用鸟苷刺激 CC 时，cGMP 的细胞内水平更高。胞外核苷酸酶和黄嘌呤氧化酶抑制剂不干扰鸟苷诱导的反应。综上所述，