The interaction of L-cysteine/hydrogen sulfide pathway and muscarinic acetylcholine receptors in mouse corpus cavernosum

The relaxant effect of hydrogen sulfide (H2S) has been demonstrated in mouse, rat, rabbit, primate and human corpus cavernosum (CC) tissues. However, the mechanism of this relaxant effect is still unclear. The aim of this study was to investigate the possible interaction of L-cysteine/H2S pathway and muscarinic receptors in the mouse CC. The relaxant responses to L-cysteine (endogenous H2S substrate;10-3M), sodium hydrogen sulfide (NaHS;exogenous H2S; 10-6–10-3 M) and acetylcholine (10-6 M) were obtained in isolated mouse CC tissues. Firstly, the effects of endogenous H2S synthesis inhibitors propargylglycine (PAG; cystathionine-gamma-lyase(CSE) inhibitor; 10–2 M), aminooxyacetic acid (AOAA; cystathionine-β-synthase(CBS) inhibitor; 10–3 M); seperately or their combination, on the relaxant response to L-cysteine and acetylcholine were investigated. PAG, but not AOAA, significantly reduced the relaxant responses to L-cysteine. PAG reduced the relaxant response to acetylcholine, while AOAA increased. The role of non-selective muscarinic receptor antagonist atropine (5x10-5 M), selective M1 antagonist pirenzepine (10-6 M), selective M2 antagonist AF-DX 116 (10-6 M) and selective M3 antagonist 4-DAMP (10-7 M) were investigated on the relaxant responses to L-cysteine, NaHS and acetylcholine in the tissues which were pre-contracted by phenylephrine (5x10-6 M). Atropine, pirenzepine and 4-DAMP, but not AF-DX 116 inhibited the relaxant responses to L-cysteine. Acetylcholine- and NaHS-induced relaxations were reduced by atropine, pirenzepine, AF-DX 116 and 4-DAMP. We conclude that L-cysteine-induced relaxant response is mediated via activation of CSE. Muscarinic receptors M1 and M3, but not M2, contributes to relaxant effect of L-cysteine in mouse CC. Also, it is shown that M1, M2 and M3 receptors play role in NaHS-induced relaxation in this tissue.