Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity.
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.
Nattie
E E
EE
Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Mills
J W
JW
Ou
L C
LC
D000818:Animals; D002245:Carbon Dioxide; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D004047:Diethyl Pyrocarbonate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D005561:Formates / Q000037:antagonists & inhibitors*; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D010890:Pirenzepine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects
D005561:Formates; D011976:Receptors, Muscarinic; D002245:Carbon Dioxide; D010890:Pirenzepine; D004047:Diethyl Pyrocarbonate