Volume 126, Issue 1, Page 179

British Journal of Pharmacology

January 1999, Volume 126, Issue 1, Pages 179 - 188

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Original Article

[³H]-Mesulergine labels 5-HT₇ sites in rat brain and guinea-pig ileum but not rat jejunum
Maggie Hemedah, Ian M. Coupar¹ & Fred J. Mitchelson
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia

¹Author for correspondence

Keywords

5-HT₇ receptor;   [³H]-mesulergine;   rat jejunum;   guinea-pig ileum;   rat brain

Abstract

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 [³H]-mesulergine, as it has a high affinity for 5-HT₇ receptors.
2   In the rat brain and guinea-pig ileum, pK_D values for [³H]-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)>sumatriptan and the antagonists risperidoneLSDmetergoline>ritanserin>>pindolol.
3   Despite the lack of [³H]-mesulergine binding in the rat jejunum, functional studies undertaken revealed a biphasic contractile response to 5-HT which was partly blocked by ondansetron (1 µM). 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 µM), cinanserin (30 nM), yohimbine (0.1 µM) and GR 113808 (1 µM). In addition, the agonist order of potency was 5-CT>5-HT>5-MeOT>sumatriptan.
4   In conclusion, binding studies performed with [³H]-mesulergine 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.

Received 18 June 1998; Revised 30 August 1998; Accepted 13 October 1998