Journal of Applied Physiology, Vol 65, Issue 5 1962-1966, Copyright © 1988 by American Physiological Society
Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity
E. E. Nattie, J. W. Mills and L. C. Ou
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Application by pledget of the M1-antimuscarinic receptor agent pirenzepine
(40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in
anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated
cats inhibited the slope of the integrated phrenic response to CO2 by 32.5%
(P less than 0.03) and the maximum value by 21.1% (P less than 0.01).
Similar application of the imidazole-histidine blocking agent diethyl
pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and
the maximum value by 29.3% (P less than 0.05). Both responses confirm
previous results. DEPC treatment decreased the effectiveness of subsequent
pirenzepine application such that although slope and maximum were further
decreased, the values were not significantly different from those after
DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory
effect. The results raise the possibility that the inhibitory effects of
DEPC on CO2 chemosensitivity are via muscarinic receptors and that
muscarinic receptor involvement in CO2 chemosensitivity requires the
presence of imidazole-histidine. Analysis by scintillation counting of
successive 100-micron sections of medulla after rostral area application of
[3H]pirenzepine indicated that the pirenzepine and DEPC effects are most
probably within 2.0 mm of the ventral surface as measured from the midline,
well away from the dorsal and ventral respiratory group neurons.
