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Title: Characterization of 5-hydroxytryptamine receptors in the snail, Helix aspersa
Author: Cadogan, Anna-Karina
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 1992
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The aim of this investigation was to characterize those 5-HT receptors present in three different tissues of the common garden snail. Helix aspersa, into one or more of the categories already described for vertebrate 5-HT receptors. Specific 5-HT receptor agonists and antagonists which had been developed and used to help characterize, and subsequently classify, the various types of 5-HT receptor in vertebrates, were utilized in this study. The three preparations from Helix included: i) identified neurones in the visceral ganglion ii) the heart and iii) the pharyngeal retractor muscle (PRM). The action of 5-HT on identified neurones in the visceral ganglion was studied using the electrophysiological techniques of both voltage- and current- damp. Under voltage-clamp conditions the response of the identified neurones to iontophoretic application of 5-HT was seen to be an inward current of approximately 3-10 nA. Under current-clamp conditions the response to 5-HT was an excitatory depolarization leading to the firing of action potentials of approximately 3-15 mV. Both responses showed rapid desensitization to repetitive applications of 5-HT and were blocked by tubocurarine. No specific 5-HT receptor antagonist to this 5-HT response in Helix neurones was found. The action of 5-HT was mimicked by 5-CT and a- Me-5-HT both of which showed similar-sized responses to 5-HT, whereas sumatriptan gave smaller responses than those of 5-HT. 5-HT had a positive inotropic effect on the heart. The excitatory action of 5-HT on the heart was studied using an organ bath methodology with application of the 5-HT receptor agonists and antagonists at suitable concentrations. No specific 5-HT receptor antagonist was found for the cardioexcitatory effect of 5-HT. The full rank order of potency for the 5-HT receptor agonists tested was 5-HT > methylergometrine = ergotamine = 5-CT > -Me-5-HT = sumatriptan > methysergide = 2-Me-5-HT = tryptamine 8-OH-DPAT. 5-HT caused relaxation in the PRM and was found to inhibit, in a dose- dependent manner, acetylcholine (ACh)-induced contraction in the muscle. This inhibition of ACh-induced contraction by 5-HT in the PRM was studied using an organ bath methodology with application of 5-HT receptor agonists and antagonists at suitable concentrations. No specific 5-HT receptor antagonist for the inhibition of ACh-induced contraction was found. The rank order of 5-HT receptor agonist potency was 5-HT > 5-CT > sumatriptan = ergotannine = methysergide >> -Me-5-HT = 2-Me-5-HT. The effect of 5-HT on cyclic adenosine 3',5'-monophosphate (cAMP) levels within Helix heart and pharyngeal retractor muscle (PRM) tissue were monitored in this investigation. 5-HT caused a dose-dependent increase in cAMP both in Helix heart and PRM tissue. The 5-HT receptors within Helix are not readily characterized into any of the categories of 5-HT receptor that have been already classified in vertebrates: Helix 5-HT receptors appear to be unique in the fact that they are unclassifiable in terms of the vertebrate 5-HT receptor classification. The evidence presented in this investigation is discussed in terms of the molecular biology of receptors: this includes the hypothesis that the 5-HT receptors particularly in Helix heart and PRM tissue could be related to a family of G-protein-coupled receptors whereas the neuronal 5-HT receptors in Helix are more likely to be integral to an ion channel.
Supervisor: Cottrell, Glen A. Sponsor: Science and Engineering Research Council (SERC) ; GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QL430.4A8C2 ; Snails