Abstract
A study was made on 211 anesthetized dogs to examine the relationship of the components of the acetylcholine-acetylcholinesterase-choline acetylase (ACh-AChE-ChA) system within the brain with the magnitude of a respiratory reflex response. The latter reflex was elicited by stimulation of Hering''s nerve, and potentiation and inhibition of the reflex was obtained by administering varying doses of the alkylphosphate, tetraethylpyrophosphate (TEPP), via cisternal puncture. A significant correlation exists between the respiratory reflex and the ACh and AChE in the cerebral cortex, midbrain, pons, and medulla. With a decreasing respiratory reflex, there is a gradual decline in the AChE activities in the brain areas, accompanied by a corresponding progressive increase in the total ACh concentrations in these areas. Small levels of ACh were associated with potentiation of the reflex, whereas elevated levels of ACh produced marked inhibition of the reflex which culminated in respiratory failure. However, no correlation was evident between the ChA activities and the respiratory reflex responses. The oximes, pyridine-2-aldoxime methiodide (PAM) and 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate (P2S), were utilized to reactivate the AChE after it had been inhibited by TEPP, which resulted in correspondingly decreased ACh concentrations but with the relationship to the reflex still evident. The evidence does not deny the existence of other factors which are presumably inherent in a process as complex as respiratory control, but these investigations do suggest that a cholinergic factor may play some active role in central respiratory reflex activity.