Anticholinesterase Activity of Acid as a Biological Instrument of Nervous Integration

Central chemosensitivity and the reaction theory.

“…This model rekindles the classical ideas of Gesell & Hansen (1942, 1945 about the role of acetylcholine in respiratory control.…”

“…By applying pledgets of tissue paper soaked with acid or alkali (Mitchell et al 1963 a, b) or by superfusion of small spots of the ventral medullary surface (Schlaefke, See & Loescheke, 1970) it was found that chemosensitivity was not uniformly effect (Gesell & Hansen 1942, 1945 distributed. Maximal drive of ventilation was observed in two areas, one medial to the vagal root and the other medial to the hypoglassal root but lateral to the pyramids.…”

Pharmacology of pH effects on carotid body chemoreceptors in vitro

“…With regard to possible effects of acid on either the release or protection of the released ACh, it is interesting to notice the following: (i) in the brain 'bound' ACh (combined with a protein) can be broken down to form 'free' ACh (diffusible) when pH falls from 7 0 to 6-5 (Mann, Tennenbaum & Quastel, 1938); (ii) potentiating effects of acid on the response to applied ACh have been demonstrated in the heart, skeletal and smooth muscle, salivary glands and respiratory centres (Gesell & Hansen, 1945); (iii) ACh is more active and stable in an acid medium because cholinesterase becomes increasingly inactivated as pH falls from 8-0 to 4-0. At the latter pH value the enzyme is practically inactive (Augustinsson, 1948).…”

Nerve and Synaptic Conduction

“…The excitability of the central nervous system to direct or reflex stimulation varies with the pH as modified by injection of buffers into the blood (45), and the effect can be assigned to the synapses traversed, not to the site of stimulation. This may be considered in relation to a previous report (46) that if the pH is held constant anoxia produces a minimum of its usually observed effects, and in relation to the effects of acid metabolites (31). Anoxia stimulates spinal cardiovascular centers directly after cord section and deafferentation, but carbon dioxide in the presence of sufficient oxygen does not stimulate (47).…”

“…Particularly in respiratory reflexes, the effects of acid me tabolites on acetylcholine as a generator of depolarizing current at the neurone surface is considered, and the experimental findings are employed to elaborate more fully the electrotonic concept of synaptic activation (31). Alterations of blood pH induce striking changes in the central nervous system, particularly in reflexes, which are decreased or abolished by increased acidity (32).…”