The role of calcium-sensing receptors in endogenous nitric oxide and hydrojen sulfide-mediated relaxiton responses in mouse corpus cavernosum smooth muscle

Erectile function is dependent on the relaxation of corpus cavernosum smooth muscle, a process in which the endogenously released gasotransmitters nitric oxide (NO) and hydrogen sulfide (H2S) play a key role. While the NO-cGMP pathway is considered the primary mechanism for erection, H2S is also known to be a potent vasodilator. Although the Calcium-Sensing Receptor (CaSR), known for its role in systemic calcium homeostasis, has been shown to regulate vascular tone, its presence in the corpus cavernosum and its modulatory effect on NO and H2S signaling pathways have not yet been fully elucidated. This thesis aimed to investigate the potential contribution of the L-cysteine/H2S pathway in CaSR-mediated relaxation responses in isolated mouse corpus cavernosum tissue. To this end, the CaSR activator Calindol was cumulatively applied to phenylephrine-precontracted tissues. The potential contribution of CaSRs to endogenous H2S-mediated relaxation was also investigated. L-cysteine (10⁻⁶-10⁻² M), a substrate for H2S synthesis, induced a concentration-dependent relaxation in phenylephrine-precontracted tissues. These cumulative relaxation responses to L-cysteine were inhibited in the presence of PAG (a CSE inhibitor) and L-NA (a NOS inhibitor). Furthermore, application of Calhex-231, a CaSR antagonist, attenuated the L-cysteine-induced relaxation responses. In conclusion, the attenuation of CSE-mediated endogenous H2S relaxation in the presence of Calhex-231 and L-NA, combined with the reduction of CaSR-mediated relaxation in the presence of a CSE inhibitor, suggests a bidirectional interaction between endogenous H2S and CaSRs. These findings also indicate that the contribution of NO to this interaction is significant.