Studies on the mode of action of bretylium and guanethidine in post-ganglionic sympathetic nerve fibres.
1. The effects of bretylium and guanethidine on the nerve terminal impulse and transmitter release from sympathetic postganglionic nerve terminals in the guinea-pig vas deferens have been studied in vitro using focal extracellular recording. Excitatory junction currents (EJCs) were used as a measure of transmitter release. 2. Both bretylium and guanethidine altered the configuration of the nerve terminal impulse in a manner consistent with their being local anaesthetics. 3. Bretylium (1-3 microM) only completely inhibited transmitter release when impulse propagation in the sympathetic nerve terminal was blocked. 4. In contrast, guanethidine (1-10 microM) could block transmitter release with little effect on the configuration of the nerve terminal impulse. 5. The inhibitory effects of these agents on both the nerve terminal impulse and on transmitter release were reversed by the indirectly acting sympathomimetic agent, d-amphetamine (1-10 microM). 6. Using this technique the mechanisms of action of drugs known to modify the transmitter release in sympathetic nerve terminals can be more precisely determined.
Brock
J A
JA
University Department of Pharmacology, Oxford, UK.
Cunnane
T C
TC
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects* / Q000502:physiology; D001949:Bretylium Compounds / Q000494:pharmacology*; D001950:Bretylium Tosylate / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004594:Electrophysiology; D006145:Guanethidine / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000294:innervation
D001949:Bretylium Compounds; D013779:Tetrodotoxin; D001950:Bretylium Tosylate; D008012:Lidocaine; D000661:Amphetamine; D003891:Desipramine; D006145:Guanethidine