Hydrogen sulfide is an oxygen sensor in the carotid body.

There is considerable controversy surrounding the initial step that transduces a fall in [Formula: see text] into a physiological signal, i.e., the "oxygen sensor" in chemoreceptors. Initial studies on systemic and respiratory vessels suggested that the metabolism of hydrogen sulfide (H(2)S) could serve as the oxygen sensor. This model was subsequently extended to chemoreceptors in fish and tissues of other animals. In this model, constitutive production of biologically active H(2)S is offset by H(2)S oxidation; when oxygen availability falls, production of H(2)S exceeds metabolism, and the resultant increase in intracellular H(2)S initiates the appropriate physiological responses. This model is supported by observations that the effects of hypoxia and H(2)S are similar, if not identical in many tissues: hypoxic responses are inhibited by inhibitors of H(2)S biosynthesis and augmented by sulfur donating molecules, and the tipping point between H(2)S production and oxidation occurs at physiologically relevant [Formula: see text] . Recent studies from other laboratories support this mechanism of O(2) sensing in the carotid body. This review summarizes information that supports the H(2)S metabolic hypothesis in these tissues with emphasis on the carotid chemoreceptors. Evidence suggesting that H(2)S is not involved in oxygen sensing in the carotid body is also critically evaluated.