[ 3 H]‐Mesulergine labels 5‐HT 7 sites in rat brain and guinea‐pig ileum but not rat jejunum

The primary aim of this investigation was to determine whether binding sites corresponding to the 5‐HT 7 receptor could be detected in smooth muscle of the rat jejunum. Binding studies in rat brain (whole brain minus cerebellum) and guinea‐pig ileal longitudinal muscle were also undertaken in order to compare the binding characteristics of these tissues. Studies were performed using [ 3 H]‐mesulergine, as it has a high affinity for 5‐HT 7 receptors. In the rat brain and guinea‐pig ileum, p K D values for [ 3 H]‐mesulergine of 8.0±0.04 and 7.9±0.11 ( n =3) and B max values of 9.9±0.3 and 21.5±4.9 fmol mg −1 protein were obtained respectively, but no binding was detected in the rat jejunum. [ 3 H]‐mesulergine binding in the rat brain and guinea‐pig ileum was displaced with the agonists 5‐carboxamidotryptamine (5‐CT)>5‐hydroxytryptamine (5‐HT)5‐methoxytryptamine (5‐MeOT)>sumatriptan and the antagonists risperidoneLSDmetergoline>ritanserin>>pindolol. Despite the lack of [ 3 H]‐mesulergine binding in the rat jejunum, functional studies undertaken revealed a biphasic contractile response to 5‐HT which was partly blocked by ondansetron (1 μ M ). The residual response was present in over 50% of tissues studied and was found to be inhibited by risperidone>LSD>metergoline>mesulergine=ritanserin>pindolol, but was unaffected by RS 102221 (3 μ M ), cinanserin (30 n M ), yohimbine (0.1 μ M ) and GR 113808 (1 μ M ). In addition, the agonist order of potency was 5‐CT>5‐HT>5‐MeOT>sumatriptan. In conclusion, binding studies performed with [ 3 H]‐mesulergine were able to detect 5‐HT 7 sites in rat brain and guinea‐pig ileum, but not in rat jejunum, where a functional 5‐HT 7 ‐like receptor was present.British Journal of Pharmacology (1999) 126 , 179–188; doi: 10.1038/sj.bjp.0702293