The interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) in mouse corpus cavernosum

• Published in: Nitric oxide Vol. 70; pp. 51 - 58
• Main Authors: Aydinoglu, Fatma, Dalkir, Fatma Tugce, Demirbag, Hatice Oruc, Ogulener, Nuran
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2017
• Subjects: Acetylcholine; Corpus cavernosum; H2S; l-cysteine; Muscarinic receptors; H2S; Acetylcholine; Corpus cavernosum; l-cysteine; Muscarinic receptors
• ISSN: 1089-8603; 1089-8611
• DOI: 10.1016/j.niox.2017.08.005

The aim of this study was to investigate the possible interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) in the mouse corpus cavernosum (CC). l-cysteine (endogenous H2S substrate; 10−6-10−3 M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10−6–10−3 M) and acetylcholine (10−9-10−4 M) produced concentration-dependent relaxation in isolated mouse CC tissues. Relaxations to endogenous and exogenous H2S were reduced by non-selective mAChR antagonist atropine (5 × 10−5 M), selective M1 mAChR antagonist pirenzepine (5 × 10−5 M) and selective M3 mAChR antagonist 4-DAMP (10−7 M) but not by selective M2 mAChR antagonist AF-DX 116 (10−6 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, 10−2 M) and cystathionine-β-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10−3 M). l-nitroarginine, nitric oxide synthase inhibitor, augmented the inhibitory effects of mAChR antagonists and H2S 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 H2S. The increase in acetylcholine level was completely inhibited by AOAA and PAG. These results suggest that M1 and M3 mAChRs contributes to relaxant effect mediated by endogenous H2S but at same time l-cysteine triggers acetylcholine release from cavernosal tissue. Also, the role of NO in the interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) could not be excluded. •CSE, CBS and 3-MST enzymes exist in mouse corpus cavernosum.•The endogenous H2S causes acetylcholine release.•CSE and CBS enzyme inhibitors reduce relaxant responses to acetylcholine.•Atropine, pirenzepine, and 4-DAMP decrease the relaxant responses to endogenous/exogenous H2S in mouse corpus cavernosum.