DRUG INDUCTION AND SUPPRESSION OF STIMULUS-BOUND REPETITION IN SYMPATHETIC GANGLIA

Bullfrog sympathetic ganglion cells, in the presence of echothiophate, neostigmine or physostigmine, exhibit a brief burst of stimulus-bound repetitive spikes (SBR) in response to an orthodromic stimulus (1/10 sec). The response to antidromic stimulation was never repetitive. The occurrence of SBR was related to drug concentration and at maximum effect, approximately 80 to 90% of cells display repetition. Increasing drug concentration beyond this point gradually suppresses SBR, and the completion of this effect merges with the beginning of transmission block. The maximal SBR caused by physostigmine may also be suppressed when d -tubocurarine or lidocaine are added to the physostigminp—Ringer's solution, in concentrations which do not block transmission. Lidocaine and d -tubocurarine begin to block transmission only after they have completely suppressed SBR. The results present distinct incompatibilities with cholinergic theory and suggest that prejunctional, direct drug actions cause induction and suppression of SBR and transmission block. By means of the complete concentration-effect data it is possible to speculate about the specific reactive groups in each drug which are responsible for the separate, although sequential, effects.