The Role of TAS2R14 Receptor in Erectile Function
Project no. 23668 · Status: Kapanmış (Yayın bekleniyor) · 2022
Summary
<p>Bitter taste receptors (TAS2R) were previously thought to be expressed only in the tongue and involved in taste perception. However, in recent studies, it has been discovered that they are also expressed in different tissues such as intestine, stomach, pancreas, including vascular smooth muscle. Also, interestingly, TAS2R agonists have been found to have relaxant effects in different smooth muscles. In the light of this information, the idea that TAS2R receptors may play a role in different biological/physiological events has come to the fore. Although TAS2R subtypes have been shown to be expressed in vascular smooth muscles and the urogenital system (bladder, uterus, testis), it is unknown whether they are expressed in penile tissue.</p><p>Erectile dysfunction (ED) is an important health problem that is accepted as an early marker of cardiovascular diseases, which increases with aging worldwide. When we screen the TAS2R subtypes targeted by agonists such as sildenafil (TAS2R14), papaverine (TAS2R7,10,14), which are used in the treatment of ED, as well as the most expressed subtypes in the vascular and urogenital system, we hypothesized that the TAS2R14 subtype may be a new therapeutic target in penile tissue. Therefore, in our study, we aimed to investigate whether Noscapine, which specifically activates 14 subtypes of TAS2Rs, and quinine and chlorpheniramine, as non-specific TAS2R14 agonists, have relaxing effects in the mouse corpus cavernosum with isolated organ bath experiments.</p><p>In our study, TAS2R14 expression in penile tissue was shown for the first time. All three agonists induced a concentration-dependent relaxation responses in the mouse penile corpus cavernosum after pre-contraction of phenylephrine (p<0.001). We also obtained relaxation responses of Quinine after U46619 pre-contraction. We found Quinine has strong relaxation responses in u46619 precontracted corpus cavernosum as well (p<0.001). Then, to investigate the role of the TAS2R14 receptor in the relaxation responses of these agonists, we tested the relaxant effect of TAS2R14 agonists in the presence of TAS2R14 antagonists. We used both specific antagonist 6-methoxyflavanone or nonspecific TAS2R14 antagonist probenesid (TAS2R14,16,38,43). Incubation with probenecid (1 mM, 30 min) or 6-methoxyflavanone (500 µM, 30 min) significantly reduced relaxation responses of all 3 agonists in pre-contracted tissues with phenylephrine (p<0.001).</p><p>In conclusion, in our study, the contribution of TAS2R14 receptors to erectile function in the mouse penile was revealed for the first time. We propose the TAS2R14 receptor subtype as a new therapeutic target in the treatment of erectile dysfunction.</p><p><br></p>