The interaction of l-cysteine/HS pathway and muscarinic acetylcholine receptors (mAChRs) in mouse corpus cavernosum.

The aim of this study was to investigate the possible interaction of l-cysteine/HS pathway and muscarinic acetylcholine receptors (mAChRs) in the mouse corpus cavernosum (CC). l-cysteine (endogenous HS substrate; 10-10 M), sodium hydrogen sulfide (NaHS; exogenous HS; 10-10 M) and acetylcholine (10-10 M) produced concentration-dependent relaxation in isolated mouse CC tissues. Relaxations to endogenous and exogenous HS were reduced by non-selective mAChR antagonist atropine (5 × 10 M), selective M mAChR antagonist pirenzepine (5 × 10 M) and selective M mAChR antagonist 4-DAMP (10 M) but not by selective M mAChR antagonist AF-DX 116 (10 M). Also, acetylcholine-induced relaxations were reduced by atropine, pirenzepine, 4-DAMP and AF-DX 116, confirming the selective effects of mAChR antagonists. Furthermore, acetylcholine-induced relaxations were attenuated by cystathionine-gamma-lyase (CSE) inhibitor d,l-propargylglycine (PAG, 10 M) and cystathionine-β-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10 M). l-nitroarginine, nitric oxide synthase inhibitor, augmented the inhibitory effects of mAChR antagonists and HS enzyme inhibitors on acetylcholine-induced relaxations. In addition, the existence and localization of CSE, CBS and 3-MST were demonstrated in mouse CC. Furthermore, tissue acetylcholine release was significantly increased by l-cysteine but not by exogenous HS. The increase in acetylcholine level was completely inhibited by AOAA and PAG. These results suggest that M and M mAChRs contributes to relaxant effect mediated by endogenous HS but at same time l-cysteine triggers acetylcholine release from cavernosal tissue. Also, the role of NO in the interaction of l-cysteine/HS pathway and muscarinic acetylcholine receptors (mAChRs) could not be excluded.