Diethyl pyrocarbonate (an imidazole binding substance) inhibits rostral VLM CO2 sensitivity.
Diethyl pyrocarbonate (DEPC) has been useful in vitro as an agent relatively specific for binding to imidazole of histidine. Administered via the cisterna magna DEPC inhibits central chemosensitivity in conscious rabbits, supporting the alphastat hypothesis for central chemoreceptor function. In this study I have applied DEPC via 1 X 3 mm cottonoid pledgets to each of the three ventrolateral medulla (VLM) chemosensitive areas in glomectomized, vagotomized, paralyzed, and servo-ventilated alpha-chloralose-urethan-anesthetized cats. CO2 responses measured by integrated phrenic nerve output were evaluated before and after DEPC application. A dose of 40 mmol/l applied to the rostral chemosensitive area increased the CO2 threshold (5.3%) and significantly decreased (P less than 0.03; Wilcoxon sign rank test) the initial slope (-43%) and the maximum (-41%) of the CO2 response. No significant effects were observed with DEPC application in the intermediate or caudal areas. Treatment with 40 mmol/l hydroxylamine immediately after DEPC in the rostral area prevented the effects supporting the interpretation that imidazole was the reactant with DEPC. The results are consistent with the hypothesis that imidazole-histidine is involved in the mechanism of central chemoreception and indicate that only the rostral area utilizes a DEPC inhibitable mechanism.
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D005260:Female; D005561:Formates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D012119:Respiration / Q000187:drug effects*
D005561:Formates; D006898:Hydroxylamines; D007093:Imidazoles; D002245:Carbon Dioxide; D019811:Hydroxylamine; D004047:Diethyl Pyrocarbonate