Studies in which the involvement of 5-HT3 heteroreceptors in modulation of ACh release has been investigated Effects of 5-HT receptor agonists or 5-HT-releasing compounds on ACh release in various brain regions and species are shown.
| Species | Brain Region | Receptor Subtypea | Drugs | Release-Modifying Concentration | Comment | References |
|---|---|---|---|---|---|---|
| Rat (Lister ♀) | Entorhinal cortex | 5-HT3 | 2-CH3-5-HT | 3 × 10–5 M: inhibition | Superfusion of slices; K+ (20 mM)-induced [3H]ACh release; inhibitory effect of 2-CH3-5-HT only in the presence of ritanserin (10–6 M); 5-HT3 antagonists GR 38032F (3 × 10–10–3 × 10–9 M) or zacopride (3 × 10–10–10–9 M) abolished the effect of 2-CH3-5-HTb | Barnes et al. (1989) |
| Guinea-pig | Cerebral neocortex | 5-HT3 | 2-CH3-5-HT | 500 μg i.c.v.: inhibition | In vivo collection of solution from epidural cup of freely moving guinea pigs; inhibition of ACh release by 5-HT [in the presence of methiothepine (2 mg/kg s.c.)] or by 2-CH3-5-HT abolished by tropisetron (0.5 mg/kg s.c.) | Bianchi et al. (1990) |
| 5-HT | 500 μg/i.c.v.: inhibition | |||||
| Cerebral neocortex | 2-CH3-5-HT | No effect | Superfusion of slices; 2-CH3-5-HT (10–5 M) without effect on electrically evoked [3H]ACh release | |||
| Guinea-pig | Cerebral neocortex | 5-HT3 | 2-CH3-5-HT | 500 μg i.c.v.: inhibition | In vivo collection of solution from epidural cup of freely moving guinea-pigs; inhibition by 2-CH3-5-HT i.c.v. or chlorimipramine s.c. prevented by MDL 72222 (1 mg/kg s.c.); chronic chlorimipramine treatment without effect (10 mg/kg daily for 14 days) | Siniscalchi et al. (1991) |
| Chlorimipramine | 10 mg/kg s.c | |||||
| Human | Neocortex synaptosomes | 5-HT3 | 5-HT | 10–8–10–6 M: inhibition | Superfusion of synaptosomes; K+ (15 mM)-induced [3H]ACh release, tropisetron (10–8–10–7 M) and ondansetron (10–7 M) blocked 5-HT-induced inhibition; 8-OH-DPAT, spiperone, and ketanserin without effect | Maura et al. (1992) |
| 1-PBG | 10–6 M: inhibition | |||||
| Rat (Sprague-Dawley ♂) | Entorhinal cortex | 5-HT3 not confirmed2 | 2-CH3-5-HT | No effect | Superfusion of slices; K+ (20 mM)-induced [3H]ACh or endogenous ACh release; 2-CH3-5-HT (10–9–10–6 M) in the presence of ritanserin (10–6 M) or ondansetron (10–9 M) without effect | Johnson et al. (1993) |
| Rat (Lister ♀) | Entorhinal cortex | 2-CH3-5-HT | Superfusion of slices; 2-CH3-5-HT (2 × 10–6 M) without effect on K+ (20 mM)-evoked [3H]ACh release | |||
| Rat (aged Wistar) | Entorhinal cortex | 2-CH3-5-HT, 5-HT | No effect | Superfusion of slices: 2-CH3-5-HT (2 × 10–6 M) without effect on K+ (20 mM)-evoked [3H]ACh release | ||
| Rat (CD ♀) | Dorsal hippocampus | 5-HT3 | d-Fenfluramine, d-norfenfluramine | 20 mg/kg i.p. increase, 7.5 mg/kg i.p.: increase | In vivo microdialysis in freely moving rats; release of endogenous ACh determined; tropisetron (0.5 mg/kg i.p.) or DAU 6215 (60 μg/kg i.p.) antagonized the norfenfluramine effect; | Consolo et al. (1994b) |
| 2-CH3-5-HT | 250 μg i.c.v. or 10–5 M by reverse dialysis: increase | DAU 6215 (60 μg/kg i.p.) or ondansetron (60 μg/kg i.p.) prevented the effects of 2-CH3-5-HT; 5-HT3 receptor antagonists, given alone, had no effect | ||||
| Rat (Wistar ♂) | Entorhinal cortex | 5-HT3 | 2-CH3-5-HT | 10–6 M: no effect | Superfusion of slices; K+ (20 mM)-induced [3H]ACh release; ondansetron and granisetron (10–8–10–5 M) enhanced spontaneous and K+-evoked [3H]ACh release; 2-CH3-5-HT counteracted the release-enhancing effect of ondansetron (10–6 M); bicuculline (10–6 M) produced potentiation of [3H]ACh release, haloperidol (10–6 M) and naloxone (10–6 M) had no effect | Ramírez et al. (1996) |
| Striatum | 1-PBG | 10–6 M: no effect | ||||
| Rat | Neocortex | 5-HT3 | mCPBG | 10–6 M: inhibition | Superfusion of synaptosomes; K+ (15 mM)-induced [3H]ACh release; VC 135 (3 × 10–8 M) blocked the effect of mCPBG | Crespi et al. (1997) |
| Rat (Wistar ♂) | Entorhinal cortex | 5-HT3 | Superfusion of slices; K+ (20 mM)-induced [3H]ACh release; ondansetron, granisetron, or MDL72222 (10–8–10–6 M) enhanced K+-evoked [3H]ACh release; bicuculline (10–7 M) or flumazenil (10–5 M) potentiated the effect of ondansetron but not of granisetron or MDL72222 | Díez-Ariza et al. (1998) |