caa a22 4500 469078669 CHVBK 20180323132943.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF00169003 doi (NATIONALLICENCE)springer-10.1007/BF00169003 A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor [Elektronische Daten] [Keith Rhodes, James Coleman, Norman Lattimer] 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. Springer-Verlag, 1992 5-HT3 receptor nationallicence 5-HT4 receptor nationallicence Vagus nerve nationallicence Ondansetron nationallicence Tropisetron nationallicence Rhodes Keith Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut Coleman James Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut Lattimer Norman Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 496-503 0028-1298 346:5<496 1992 346 210 https://doi.org/10.1007/BF00169003 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00169003 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rhodes Keith Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut NATIONALLICENCE 700 1- Coleman James Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut NATIONALLICENCE 700 1- Lattimer Norman Department of Biomedical Research, Wyeth Research (UK) Ltd., Huntercombe Lane South, SL6 OPH, Taplow, Maidenhead, Berkshire, UK aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/5(1992-11-01), 496-503 0028-1298 346:5<496 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer