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A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor

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Summary

This study describes a component of 5-HT-evoked depolarization of the rat isolated vagus nerve which was unaffected by the 5-HT3 receptor antagonist ondansetron. A grease-gap extracellular recording technique was used. Ondansetron (10–100 nmol/1) displaced the 5-HT concentration-response curve to the right yielding a pA2 value of 8.6 (8.5–8.8), consistent with 5-HT3 receptor antagonism, and revealing a component of the 5-HT response which was resistant to ondansetron blockade. In the presence of ondansetron (100 nmol/1) the maximum depolarization in the resistant phase was 15.5 (12.6–19.2)% of the initial maximum response to 5-HT and the pEC50 value was 7.0 (6.7–7.3). The mechanism of the ondansetron-resistant component of the 5-HT response resembled a 5-HT4 -receptor-effect in being absent in preparations equilibrated with 5-methoxytryptamine (10 μmol/1) and antagonised by ICS 205930 (tropisetron, pA2 6.4). 5-Methoxytryptamine alone was an agonist in the vagus nerve with a maximum response similar to that of the ondansetron resistant phase of the 5-HT response. similarly renzapride alone evoked small depolarizations of this preparation but antagonized the ondansetron resistant phase of the 5-HT response (pA2 7.3–7.4). These effects of 5-methoxytryptamine and renzapride are also consistent with a 5-HT4 receptor mechanism. Ketanserin (1 μmol/1) and methysergide (1 μmol/1) had little effect on responses to 5-HT. The depolarization evoked by this putative 5-HT4 receptor mechanism was small but prolonged and appears to mask and after-hyperpolarizing phase of the 5-HT response in this tissue.

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Authors and Affiliations

  1. Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK

    Keith F. Rhodes, James Coleman & Norman Lattimer

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  1. Keith F. Rhodes
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  2. James Coleman
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  3. Norman Lattimer
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Correspondence to: K. F. Rhodes at the above address

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Rhodes, K.F., Coleman, J. & Lattimer, N. A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor. Naunyn-Schmiedeberg's Arch Pharmacol 346, 496–503 (1992). https://doi.org/10.1007/BF00169003

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  • DOI: https://doi.org/10.1007/BF00169003

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