Effects of 2-deoxy-D-glucose on in vitro cat carotid body

The process of chemosensory transduction in the arterial chemoreceptors is not well understood. According to the metabolic hypothesis of chemoreception, a decrease in arterial pO2 will produce a decrease in the adenosine triphosphate (ATP) content in the chemosensory type I cells, leading to release of a neurotransmitter and increased sensory neural activity. There is a paucity of direct experimental support for this hypothesis, and in the present work, we have tested the postulates of the metabolic hypothesis in an in vitro preparation of cat carotid body using 2-deoxy-D-glucose as an ATP-depleting agent. This preparation, when superfused with Tyrode containing 5 mM Na+-pyruvate instead of glucose, responds normally to hypoxia, low pH and acetylcholine, and maintains normal ATP levels. Under these conditions, 2-deoxy-D-glucose is a chemostimulant, i.e. electrical activity in the carotid sinus nerve is increased, with a threshold concentration of 0.25 mM and a maximum response at about 2-4 mM. These concentrations of 2-deoxyglucose evoke a dose-dependent release of [3H]dopamine (synthesized from [3H]tyrosine) from the carotid bodies which parallels the electrical activity. The 2-deoxy-D-glucose-evoked release and electrical activity is dependent on the presence of extracellular Ca2+. These same concentrations of 2-deoxy-D-glucose significantly reduce the ATP content of the carotid bodies. The events postulated by the metabolic hypothesis, i.e. decrease in ATP content, release of a putative neurotransmitter and activation of the sensory nerve endings are found to occur simultaneously. A possible cause-effect relationship between these three events is discussed.