A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor.
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/l) 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/l) 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 mumol/l) 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 mumol/l) and methysergide (1 mumol/l) 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.
Rhodes
K F
KF
Department of Biomedical Research, Wyeth Research Ltd., Maidenhead, Berkshire, UK.
Coleman
J
J
Lattimer
N
N
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D066298:In Vitro Techniques; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology; D011199:Potentiometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009467:Neuromuscular Depolarizing Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D008735:5-Methoxytryptamine; D017294:Ondansetron; C045918:2-methyl-5-HT; C053006:renzapride