Expression and activity of the umami taste receptor (TAS1R1/TAS1R3) in rat corpus cavernosum.

The activation of umami taste receptors (TAS1R1/TAS1R3) promotes smooth muscle (SM) relaxation in the mouse stomach. The nitric oxide (NO)/cGMP signaling pathway is crucial for penile erection. Phosphodiesterase type 5 (PDE5) inhibitors, which specifically target cGMP, are the primary treatment for erectile dysfunction (ED). However, these drugs are ineffective in a significant number of patients, highlighting the need for alternative pharmacological targets for ED. Since umami taste receptors regulate SM contractility, this study investigates the role of TAS1R1/TAS1R3 in rat erectile tissue. We performed immunohistochemistry on the corpus cavernosum (CC) and dorsal penile artery (DPA) to detect TAS1R1/TAS1R3 expression. Isometric force recordings for the TAS1R1/TAS1R3 agonist monosodium glutamate (MSG), the NO donor SNAP, the hydrogen sulfide (H2S) donor GYY 4137, and electrical field stimulation (EFS) and measured endogenous H2S production. Immunohistochemistry revealed strong TAS1R1/TAS1R3 expression in nerve fibers of the CC and in the endothelium of the DPA, with limited expression in SM. In the CC, MSG enhanced relaxations induced by EFS, SNAP, and GYY 4137, and increased H2S production, which was sensitive to NO and H2S synthase inhibitors. MSG-induced relaxation was reduced by inhibition of neuronal voltage-gated calcium channels. In the DPA, MSG induced relaxation which was reduced by mechanical removal of the endothelium. These findings indicate significant neuronal and endothelial expression of TAS1R1/TAS1R3 in the CC and DPA, where MSG promotes SM relaxation. In the CC, MSG enhances nerve-mediated relaxation induced by NO and H2S and stimulates H2S production, suggesting TAS1R1/TAS1R3 as a potential therapeutic target for ED.