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

Citation
C. Roberts et al., The effect of SB-269970, a 5-HT7 receptor antagonist, on 5-HT release fromserotonergic terminals and cell bodies, BR J PHARM, 132(7), 2001, pp. 1574-1580
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
0007-1188 → ACNP
Volume
132
Issue
7
Year of publication
2001
Pages
1574 - 1580
Database
ISI
SICI code
0007-1188(200104)132:7<1574:TEOSA5>2.0.ZU;2-D
Abstract
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 effec t of the 5-HT7 receptor antagonist, SB-269970 ((R)-1-[3-hydroxy phenyl)sulf onyl]-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 nuc leus (DRN), using the techniques of in vitro [H-3]-5-HT release or fast cyc lic voltammetry, respectively. 2 Cortical slices were loaded with [H-3]-5-HT and release was evoked by ele ctrical stimulation. 5-CT inhibited the evoked release of [H-3]-5-HT in a c oncentration-dependent manner. SE-269970 had no significant effect on [H-3] -5-HT release while the 5-HT1B receptor antagonist, SB-224289 significantly potentiated [H-3]-5-HT release. In addition, SE-269970 was unable to atten uate the 5-CT-induced inhibition of release while SB-224289 produced a righ tward shift of the 5-CT response, generating estimated pK(B) 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 de tected 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 e fflux pet se or 8-OH-DPAT-induced inhibition of 5-HT efflux. In addition, 5 -CT inhibited 5-HT efflux in a concentration-dependent manner. SE-269970 wa s 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 autor eceptor role for 5-HT7 receptors. However, investigations with more selecti ve 5-HT7 receptor agonists are needed to confirm the data reported here.