Involvement of RhoA/Rho-kinase in L-cysteine/H 2 S pathway-induced inhibition of agonist-mediated corpus cavernosal smooth muscle contraction

PubMedID: 30768962Rho-kinase activity is a key regulator in the maintenance of corporal vasoconstriction and penile detumescense. Also, importance of L-cysteine/H 2 S pathway in erectile tissue has been shown; however it is currently unknown the role RhoA/Rho-kinase pathway in H 2 S-induced inhibition in cavernosal tissue. We investigated the role of RhoA/Rho-kinase pathway in the inhibitory effect of L-cysteine and NaHS, as endogenous and exogenous H 2 S, respectively, on phenylephrine-induced contractions of mouse cavernosal strips. Phenylephrine, ? 1 receptor agonist, (10 nM-100 µM) induced a concentration-dependent contraction in CC. L-cysteine (endogenous H 2 S substrate; 10 mM) and exogenous H 2 S (NaHS; 1 mM) significantly inhibited the contractile response to phenylephrine (P < 0.05). Inhibition of CSE and CBS enzymes by PAG (10 mM) and AOAA (1 mM), respectively, significantly reversed the inhibitory effects of L-cysteine on phenylephrine-induced contraction (P < 0.05). Y-27632 (1 µM), a specific Rho-kinase inhibitor, significantly augmented the inhibitory effect of L-cysteine and NaHS on phenylephrine-induced contraction, and this inhibition was reversed by PAG and AOAA (P < 0.05). In addition, the formation of H 2 S was increased by approximately 1.8 fold over basal values after incubation of tissue homogenates with L-cysteine. Y-27632 significantly increased both basal and L-cysteine-induced H 2 S formation and this augmentation diminished by PAG and AOAA (P < 0.05). Furthermore, the pMYPT-1 expression was significantly decreased by L-cysteine, NaHS or Y-27632 alone. Also, pMYPT-1 expression was completely abolished by the L-cysteine/NaHS plus Y-27632 combination, and this inhibition was reversed by PAG and AOAA (P < 0.05). These results suggest that there is an interaction between Rho-kinase and H 2 S pathways. Rho-kinase may be, at least in part, inhibits CSE/CBS enzymes in mouse corpus cavernosal tissue; however, it is not excluded the other kinases such as PKC and Zip-kinase. © 2019 Elsevier Inc.TF2013BAP2This study was supported by Cukurova University Research Foundation ( TF2013BAP2 )