Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, 13083-881, Brazil.
Purinergic Signal. 2020 Jun;16(2):241-249. doi: 10.1007/s11302-020-09702-5. Epub 2020 May 27.
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.
在海绵体（CC）中，三磷酸鸟苷（GTP）转化为环鸟苷单磷酸（cGMP）以诱导勃起。cGMP 的作用通过磷酸二酯酶和外排转运蛋白终止，这些酶将 cGMP 泵出细胞。核苷酸 GTP 和 cGMP 被检测到细胞外空间中，它们的水解导致中间产物的形成，其中包括鸟苷。因此，我们的研究旨在从老鼠的 CC 中对鸟苷的作用进行药理学表征。分离阴茎并进行功能和生化分析。基于鸟嘌呤的核苷酸 GTP、鸟苷二磷酸、鸟苷单磷酸和 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（约 45%，P<0.05）。在存在腺苷 2A 和 2B 受体拮抗剂的情况下，鸟苷诱导的松弛没有改变。用鸟苷刺激组织时，细胞内环腺苷单磷酸的水平没有增加。一氧化氮合酶抑制剂（L-NAME，100 μM）和可溶性鸟苷酸环化酶抑制剂（ODQ，10 μM）在所有研究浓度下均显著降低了鸟苷诱导的松弛，而在他达拉非（300 nM）存在下，观察到显著增加。鸟苷（100 μM）的预孵育导致他达拉非诱导松弛产生 6.6 左移。当 CC 受到鸟苷刺激时，cGMP 的细胞内水平增加。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。结论是，我们的研究表明鸟苷使小鼠 CC 松弛，并为测试其在勃起功能障碍模型中的作用提供了可能性。
