Effects of guanethidine and phenethylguanidine on the frog neuromuscular junction.
The effects of two guanidine derivatives, guanethidine and phenethylguanidine (2-phenyl-ethyl-guanidine), on neuromuscular transmission in the sartorius nerve-muscle preparation of the frog, Rana pipiens, were investigated. Both compounds decreased the peak height of the evoked end-plate current (EPC). The decay of the EPC was changed from a single exponential to a double exponential. The effects of both compounds on the EPC peak height increased with hyperpolarization, and the peak EPC/membrane voltage relationship thus became non-linear. The absence of an effect on the mean quantal content (m) indicated that the two compounds acted postsynaptically. The power spectrum of the ACh-induced noise was changed by guanethidine from a single Lorentzian to a double Lorentzian curve. The single channel conductance was decreased with hyperpolarization. It was concluded from these observations that guanethidine is an open channel blocker. Phenethylguanidine shifted the cut-off frequency of the ACh-induced noise to a higher frequency. However, the power spectrum showed only a single Lorentzian, and there was a lack of low frequency component in the power spectrum, which was expected from the decay phase of the EPC. The single channel conductance decreased, but in contrast to the case of guanethidine, there was no voltage dependency. The possible mechanism of action of phenethylguanidine is discussed.
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Enomoto
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Maeno
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Edwards
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006145:Guanethidine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008433:Mathematics; D009045:Motor Endplate / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D010629:Phenformin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011894:Rana pipiens; D011950:Receptors, Cholinergic / Q000187:drug effects
D007473:Ion Channels; D011950:Receptors, Cholinergic; C008830:phenethylguanidine; D010629:Phenformin; D000109:Acetylcholine; D006145:Guanethidine