Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor

Abstract

SUMMARY Hydrogen sulfide (H2S) has been shown to affect gastrointestinal (GI) motility and signaling in mammals and O2-dependent H2S metabolism has been proposed to serve as an O2 ‘sensor’ that couples hypoxic stimuli to effector responses in a variety of other O2-sensing tissues. The low PO2 values and high H2S concentrations routinely encountered in the GI tract suggest that H2S might also be involved in hypoxic responses in these tissues. In the present study we examined the effect of H2S on stomach, esophagus, gallbladder and intestinal motility in the rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch) and we evaluated the potential for H2S in oxygen sensing by examining GI responses to hypoxia in the presence of known inhibitors of H2S biosynthesis and by adding the sulfide donor cysteine (Cys). We also measured H2S production by intestinal tissue in real time and in the presence and absence of oxygen. In tissues exhibiting spontaneous contractions, H2S inhibited contraction magnitude (area under the curve and amplitude) and frequency, and in all tissues it reduced baseline tension in a concentration-dependent relationship. Longitudinal intestinal smooth muscle was significantly more sensitive to H2S than other tissues, exhibiting significant inhibitory responses at 1–10 μmol l–1 H2S. The effects of hypoxia were essentially identical to those of H2S in longitudinal and circular intestinal smooth muscle; of special note was a unique transient stimulatory effect upon application of both hypoxia and H2S. Inhibitors of enzymes implicated in H2S biosynthesis (cystathionine β-synthase and cystathionine γ-lyase) partially inhibited the effects of hypoxia whereas the hypoxic effects were augmented by the sulfide donor Cys. Furthermore, tissue production of H2S was inversely related to O2; addition of Cys to intestinal tissue homogenate stimulated H2S production when the tissue was gassed with 100% nitrogen (∼0% O2), whereas addition of oxygen (∼10% O2) reversed this to net H2S consumption. This study shows that the inhibitory effects of H2S on the GI tract of a non-mammalian vertebrate are identical to those reported in mammals and they provide further evidence that H2S is a key mediator of the hypoxic response in a variety of O2-sensitive tissues.