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Title: The Hermit crab (Eupagurus bernhardus) neuromuscular junction : a pharmacological investigation
Author: McBain, Anne Elizabeth
ISNI:       0000 0001 3622 5541
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1983
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Intracellular recordings were made from the opener muscle in the walkleg of the Hermit crab (Eupagurus bernhardus). Stimulation of either the excitatory or inhibitory nerve bundle evoked excitatory (EJP) and inhibitory (IJP) junction potentials respectively. Two characteristics of junction potentials were recorded, facilitating and non-facilitating glutamate depolarized the muscle fibre membrane. Evidence is presented which suggests that this amino acid plays a role in excitatory trananission at the Hermit crab NMJ. The structure-activity relations between a variety of conformationally restricted glutamate arale .:es such as DL-ibotenic acid, the piperidine dicarboxylates and e)v_c.entanes and the excitatory receptor suggested that L-glutamate ~n:enacted in a partially folded conformation. Threshold concentra.os of L-glutamate and two other agonists, quisqulaic acid and kainic acid, potentiated both the EJPs and the glutamate potential. A tarzrcological discrepancy between the effects of DL-homocysteic acid and dihydrokainic acid on the EJPs and the glutamate potential was revealed. The effects of kainic acid and a-ketokainic acid suggested the existence of heterogenous excitatory receptor populations. =n addition, a novel hyperpolarization and biphasic response to L-glutamate and cis and trans cyclopentanes was described. Several compounds, including GDEE, DLaaa and the phosphonic analogues of L-glutamate antagonized both the evoked EJPs and the glutamate potential. However, many of these compounds had non-specific effects which rendered them unsuitable as antagonists. A kinetics of the onset and recovery from glutamate receptor desensitization were examined. No evidence was obtained for an effect of calcium on either the rate of onset or recovery. The piperidine dicarboxylate analogues reversibly prevented the development of glutars:e receptor desensitization. Concanavalin A irreversibly abolished desensitization.3a; did not produce an effect on the membrane potential but decreased the fibre input resistance. The GABA response was mediated =ainl, by chloride ions. The structure-activity relationship of GAFA an-4 its analogues TRIP and isoguvacine with the inhibitory receptor supports the view that GABA interacts with the receptor in a more extended configuration. The uptake inhibitors nipecotic acid and gLvacine enhanced the effect of GABA. Picrotoxin and bicuculline antagor:sed both GABA and the IJPs. Bicuculline was leas potent than picrotoxin as an antagonist of GABA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry