EFFECTS OF ENERGY DONORS, METABOLIC INHIBITORS AND SUBSTRATES ON CAROTID CHEMORECEPTOR ACTIVITY

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Carotid chemoreceptor activity was studied electrically, as affected by the intracarotid injection of agents related to carbohydrate metabolism.

All high-energy phosphates tested (ATP, AMP and pyrophosphate) excited chemoreceptors after a variable latent period (concentrations of 0.2 micromols/ml. or higher). ATP alone displayed a strong "early" as well as the variable "late" chemoreceptor excitatory action. NaH₂PO₄ enhanced activity only if given in enormously higher concentrations (20 micromols/ mi.).

Azide displayed excitatory action similar to (and competitive to) cyanide; selective inhibition of anoxic stimuli with relatively unchanged responsiveness to cholinergic ones was present after moderate amounts of azide; large doses were followed by complete unresponsiveness to any stimulus.

Thiopental and pentobarbital depressed, whereas a convulsant barbiturate and 2, 4-dinitrophenol enhanced chemoreceptor activity.

Glucose and several other products of carbohydrate metabolism depressed chemoreceptor activity for periods up to 10 seconds, and a moderate rebound, lasting several seconds, was observed thereafter. The late chemoreceptor rebound was less marked with high concentrations of substrates and both responses were present following injections of sucrose (non-metabolized).

The results are analyzed on the basis of current concepts of chemoreceptor excitation and with regard to the hypothesis of depression of oxidative phosphorylation as a stimulus for chemoreceptor activation. The data show that several excitatory mechanisms may operate and that "uncoupling" agents may have diametrically opposite action on these receptors.