Intracisternal diethylpyrocarbonate inhibits central chemosensitivity in conscious rabbits

Abstract

As a direct chemical test of the alpha-imidazole hypothesis for the function of mammalian central chemoreceptors (CCR), diethylprocarbonate (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 fashio, induced resting hypoventilation and inhibited (1) the ventilatory response to CO 2 in peripherally chemodenervated animals, and (2) both the Pa CO 2 and minute ventilation responses to ICM infusion of an acidic mock cerebrospinal fluid (CSF). HEPC had no effect on the hypoxic ventilatory response and had small non-dose-dependent effects on body temperature. ICM adminstration 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.