FACILITATION OF GANGLIONIC TRANSMISSION FOLLOWING INHIBITION OF CHOLINESTERASE BY DFP

¹ Departments of Anesthesiology and Pharmacology, Columbia University, College of Physicians and Surgeons, New York 32, N. Y.
² Department of Physiology and Pharmacology, Graduate School of Medicine, University of Pennsylvania, Philadelphia, Pa.

The effects of DFP on axonal conduction and ganglionic transmission were investigated by examining the pre- and post-synaptic action potentials of normally circulated superior cervical ganglia of cats and isolated superior cervical ganglia of rats. Graded stimuli of several frequencies were delivered to the preganglionic trunks. Results were correlated with estimated inactivations of specific and nonspecific cholinesterases.

The postganglionic responses of non-atropinized cat ganglia to submaximal volleys were increased following doses of DFP (0.25-2.0 mgm./kgm.) which completely inactivate nonspecific cholinesterase, and which inactivate a major portion of specific cholinesterase. Responses to infrequent maximal volleys were not appreciably affected. Following higher doses of DFP (4-8 mgm./kgm.) depression of ganglionic, and subsequently, of preganglionic responses generally occurred. Atropine, 5 mgm./kgm. i.v. produced significant and lasting depression of ganglionic responses. DFP in doses up to 3 mgm./kgm. effectively overcame depression by atropine.

Immersion of excised rat ganglia in concentrations of DFP which caused complete inactivation of nonspecific cholinesterase and partial inactivation of specific cholinesterase was followed by inconstant facilitation of ganglionic responses to low frequency preganglionic volleys. Responses to submaximal volleys were more frequently and more strikingly increased than were responses to maximal volleys. Immersion of ganglia in concentrations of DFP which caused more nearly complete inactivation of specific cholinesterase resulted in depression of ganglionic responses. After-discharge was observed consistently following immersion in 10^-5 M DFP, a concentration of DFP which usually caused practically complete inactivation of specific cholinesterase.

The foregoing results are consistent with the hypothesis that facilitation of ganglionic transmission following DFP is due primarily to inactivation of specific cholinesterase. The dose ranges producing such had no consistent effect on preganglionic conduction. The depressant effect of higher doses of DFP on transmission and conduction is probably due to an action unrelated to its anticholinesterase effect. Possible mechanisms are discussed.