Intracisternal diethylpyrocarbonate inhibits central chemosensitivity in conscious rabbits

As a direct chemical test of the alpha-imidazole hypothesis for the function of mammalian central chemoreceptors (CCR), diethylpyrocarbonate (DEPC) a relatively specific reactant with imidazole groups in vitro has been administered in vivo via intracisterna magna (ICM) infusion in conscious rabbits using each rabbit as its own control. DEPC, in a dose-dependent fashion, induced resting hypoventilation and inhibited (1) the ventilatory response to CO2 in peripherally chemodenervated animals, and (2) both the PaCO2 and minute ventilation responses to ICM infusion of an acidic mock cerebrospinal fluid (CSF). DEPC had no effect on the hypoxic ventilatory response and had small non-dose-dependent effects on body temperature. ICM administration of hydroxylamine (HDA), a substance that reverses the DEPC-imidazole binding in vitro, prevented DEPC induced inhibition of CCR function. These data support but do not prove the alpha-imidazole hypothesis for mammalian central chemoreceptor function and demonstrate a potentially useful chemical tool for the study of central chemoreception.