[3H]-mesulergine labels 5-HT7 sites in rat brain and guinea-pig ileum but not rat jejunum

1 The primary aim of this investigation was to determine whether binding sites corresponding to the 5-HT7 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 [H-3]-mesulergine, as it has a high affinity for 5-HT7 receptors. 2 In the rat brain and guinea-pig ileum, pK(D) values for [H-3]-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. [3H]-mesulergine binding in the rat brain and guinea-pig ileum was displaced with the agonists 5-carboxamidotryptamine (5-CT) > 5-hydroxytryptamine (5-HT) greater than or equal to 5-methoxytryptamine (5-MeOT) s sumatriptan and the antagonists risperidone greater than or equal to LSD greater than or equal to metergoline > ritanserin > > pindolol. 3 Despite the lack of [H-3]-mesulergine binding in the rat jejunum, functional studies undertaken revealed a biphasic contractile response to 5-HT which was partly blocked by ondansetron (1 mu 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 mu M), cinanserin (30 nM), yohimbine (0.1 mu M) and GR 113808 (1 mu M). In addition, the agonist order of potency was 5-CT > 5-HT > 5-MeOT > sumatriptan. 4 In conclusion, binding studies performed with [H-3]-mesulergime were able to detect 5-HT7 sites in rat brain and guinea-pig ileum, but not in rat jejunum, where a functional 5-HT7-like receptor was present.