ATP activates phospholipase C in the cat carotid body in vitro.

In this study we investigated the hypothesis that ATP could play a role in the transduction of the hypoxic stimulus in the carotid body (CB) by being a regulator of the phosphatidylinositol-4,5-bisphosphate (PIP2)-specific phospholipase C (PLC). We addressed this question by comparing the PLC activity in the absence and presence of ATP in homogenates of CBs dissected from anesthetized cats that were preexposed in vivo to the contrasting conditions of normoxia (PaO2 approximately 90 mmHg) and hypoxia (PaO2 approximately 20 mmHg). The tissue of a nearby superior cervical ganglion (SCG) was used as a reference. The homogenate was the source of PLC. PLC activity was assayed by measuring the formation of radioactive inositol 1,4,5-trisphosphate from [3H]PIP2, used as an exogenous substrate. ATP was added to the assay mixture at the concentrations of 0.25 mM and 1 mM, chosen on the basis of test trials on ATP dependence of PLC changes. We found that ATP increased appreciably the PLC activity over its basal (absence of ATP) level in the normoxic carotid body. The stimulatory effect of ATP was augmented in the hypoxic carotid body, the lower ATP concentration having a stronger effect. Such PLC changes were absent in the SCG. These findings suggest a regulatory role for ATP in the PLC-linked hypoxic signal transduction in the carotid body.