The effect of SB-269970, a 5-HT7 receptor antagonist, on 5-HT release from serotonergic terminals and cell bodies

Claire Roberts, Lucy Allen, Christopher J. Langmead, Jim J. Hagan, Derek N. Middlemiss, Gary W. Price

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1. The presence of 5-HT7 receptor mRNA and protein in 5-HT neurons suggests that this receptor may act as a 5-HT autoreceptor. In this study, the effect of the 5-HT7 receptor antagonist, SB-269970 ((R)-1-[3-hydroxy phenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine), was investigated on 5-HT release in the guinea-pig and rat cortex and the rat dorsal raphe nucleus (DRN), using the techniques of in vitro [3H]-5-HT release or fast cyclic voltammetry, respectively. 2. Cortical slices were loaded with [3H]-5-HT and release was evoked by electrical stimulation. 5-CT inhibited the evoked release of [3H]-5-HT in a concentration-dependent manner. SB-269970 had no significant effect on [3H]-5-HT release while the 5-HT1B receptor antagonist, SB-224289 significantly potentiated [3H]-5-HT release. In addition, SB-269970 was unable to attenuate the 5-CT-induced inhibition of release while SB-224289 produced a rightward shift of the 5-CT response, generating estimated pKB values of 7.8 and 7.6 at the guinea-pig and rat terminal 5-HT autoreceptors respectively. 3. Rat DRN slices were electrically stimulated and the evoked 5-HT efflux detected by voltammetric analysis. 8-OH-DPAT inhibited evoked 5-HT efflux and was fully reversed by WAY 100635. SB-269970 had no effect on either 5-HT efflux per se or 8-OH-DPAT-induced inhibition of 5-HT efflux. In addition, 5-CT inhibited 5-HT efflux in a concentration-dependent manner. SB-269970 was unable to attenuate the 5-CT-induced inhibition of 5-HT efflux. 4. In conclusion, we were unable to provide evidence to suggest a 5-HT autoreceptor role for 5-HT7 receptors. However, investigations with more selective 5-HT7 receptor agonists are needed to confirm the data reported here.

Original languageEnglish
Pages (from-to)1574-1580
Number of pages7
JournalBritish Journal of Pharmacology
Issue number7
Publication statusPublished - 1 Jan 2001
Externally publishedYes


  • Voltammetry

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