NERVE-DIAPHRAGM PREPARATION OF THE RAT

Abstract

The phenomenon of drug-induced facilitation of the indirectly elicited muscle twitch has been studied by a number of authors. Both pro-and poatsynaptic sites have been implicated in the fadiitatory process ; the greater emphasis has been placed on presynaptic actions (Werner, 1960; Standaert and Biker, 1967 ; Karczmar, 1967). The occurrence of this phenomenon in the isolated phrenic nerve-diaphragm preparation of the rat (Bilibring, 1946) action of fadilitatory drugs was studied in the phrenic nerve-diaphragmpreparation and the chronically denervated diaphragm of the rat. The latter was used as a model of the post synaptic receptor. The drugs were tetrahydro4.aminoacridine and a series of hydroxy anilinium compounds which included edrophonium. The drugs caused twitch potentiation and spontaneous activity in the intact preparation; these effects were depressed by temperature reduction, low Ca@ solutions or high Mg@ solutions. The acetylcholine con traction of the denervated diaphragm was potentiated by all drugs except 3-hydroxyphenyl First, this receptor is easy to approach experi mentally ; drug concentrations and ionic levels can be maintained as required. Second, it con tains acetylcholinesterase only in the region of the degenerating synapse (Eränkà ¶ and Terä väinen,1967). The effects of four fadiitatory drugs have been determined on the innervated and the denervated preparation. In addition, interactions with succinyicholine (SCh) have been studied to determine the role of facilitatory processes in the relief of SCh blockade. The drugs studied are a series of hydroxy anhinium compounds which includes edropho nium and the structurally unrelated compound tetrahydro-4-aminoacridine (tacrine). The study offers evidence of pro-and postsynaptic actions of these compounds and permits tentative con clusions as to the structural features of the series. 56