Guanosine, a guanine-based nucleoside relaxed isolated corpus cavernosum from mice through cGMP accumulation

Author(s)

Nicoletti, Aline de Souza ^[1] ; Passos, Gabriela Reolon ^[1] ; Bertollotto, Gabriela Maria ^[1] ; Lescano, Caroline Honaiser ^[1] ; de Oliveira, Mariana Goncalves ^[1] ; Antunes, Edson ^[1] ; Monica, Fabiola Zakia ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, BR-13083881 Campinas, SP - Brazil

• Document type: Journal article
• Source: PURINERGIC SIGNALLING; v. 16, n. 2 MAY 2020.
• Web of Science Citations: 0

Abstract

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 (similar to 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 mu M) and soluble guanylate cyclase (ODQ, 10 mu M) 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 mu M) 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. (AU)

• FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
• Grantee: Edson Antunes
• Support Opportunities: Research Projects - Thematic Grants