Nitric oxide : biology and chemistry, vol.119, pp.19-28, 2021 (SCI-Expanded)
In this study, we investigated the possible role of the L-cysteine/hydrogen sulfide pathway in beta(3)-adrenoceptors-mediated relaxation in isolated mouse gastric fundus tissue. L-cysteine (endogenous H2S; 10(-6)-10(-2) M), sodium hydrogen sulfide (NaHS; exogenous H2S; 10(-6)-10(-3) M), selective beta(3)-adrenoceptors agonist BRL 37344 (10(-9)-10(-4) M) and non-selective beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M) produced concentration-dependent relaxation in mouse gastric fundus. The non-selective beta-adrenoceptors antagonist propranolol (10(-6) M) inhibited the relaxant response to isoprenaline but not to BRL 37344. On the other hand, the selective beta(3)-adrenoceptors antagonist SR 59230A (10(-5) M) inhibited the relaxant responses to BRL 37344. In addition, cystathionine-gamma-lyase (CSE) inhibitor D,L-propargylglycine (PAG, 10(-2) M), cystathionine-beta-synthase inhibitor (CBS) aminooxyacetic acid (AOAA, 10(-2) M), and the combination of these inhibitors significantly reduced the relaxant responses induced by L-cysteine and BRL 37344. Pre-incubation of gastric fundal strips with propranolol (10(-6) M) and SR 59230A (10(-5) M) did not affect relaxations to L-cysteine and NaHS. Also, the existence of CSE, CBS, 3-mercaptopurivate sulfur transferase (3-MST) enzymes and beta(3)-adrenoceptors were detected in gastric fundal tissue. Furthermore, basal H2S release was detected in the measurements. H2S level increased in the presence of L-cysteine, NaHS, and BRL 37344. The increase in H2S level by L-cysteine and BRL 37344 decreased significantly with PAG and AOAA enzyme inhibitors. These results suggest that endogenous H2S is synthesized from L-cysteine at least by CBS and CSE enzymes. Also, beta(3)-adrenoceptors are found in the mouse stomach fundus and mediate BRL 37344-induced relaxations, and L-cysteine/hydrogen sulfide pathway plays a partial role in beta(3)-adrenoceptors-mediated relaxation in mouse gastric fundus tissue.