Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding

Abstract

Functional serotonin (5-hydroxytryptamine, 5-HT) receptors have been divided into three subtypes: 5-HT1-like, 5-HT2 and 5-HT3 (ref. 1). Brain binding sites have been identified for both the 5-HT1 and 5-HT2 subtypes. Receptors of the 5-HT3 type have been characterized on isolated peripheral tissue models such as the rat vagus nerve, guinea-pig ileum and isolated rabbit heart. Using these models, selective 5-HT3 receptor antagonists such as MDL 72222 (ref. 5), ICS 205-930 (ref. 6), GR38032F (ref. 7) and BRL 43694 (ref. 8) have been developed. Recently, GR38032F, MDL 72222 and ICS 205-930 have been shown to have behavioural effects in rodents and primates that undoubtedly reflect an action in the central nervous system (refs 9-11 and unpublished observations), suggesting the existence of 5-HT3 receptors in the brain. Here we report direct evidence for the existence of 5-HT3 receptors in rat brain tissue and their distribution, based on high affinity binding of the potent 5-HT3 receptor antagonist 3H-GR65630 to homogenates of rat entorhinal cortex. Selective 5-HT3 receptor antagonists and agonists inhibited binding of 3H-GR65630 with high affinities which correlated well with their actions on the rat isolated vagus nerve. Binding was differentially distributed throughout the brain with high concentrations in cortical and limbic areas.

Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

“…In this study, ICS-205-930 strongly inhibited EM523 as well as motilin-induced gas tric contractions. 5HT3 receptors are reported to be dis tributed in the area postrema (12)(13)(14), the enteric nervous system (15)(16)(17) and afferent vagus nerves (14,17,18) in ferrets, rats and guinea pigs. Boeckxstaens et al (19) reported that stimulation of the 5HT3 receptors resulted in acetylcholine-mediated contractions through choliner gic efferent nerves in the canine ileal myenteric plexus.…”

Cholecystokinin release mediated by 5‐HT3 receptors in rat cerebral cortex and nucleus accumbens

“…Evidence from radioligand binding studies (Kilpatrick et al, 1987;Peroutka & Hamik, 1988;Waeber et al, 1989) and behavioural tests (Costall et al, 1987;Jones et al, 1988) have shown that 5-HT3 receptors exist not only in the periphery but also in the central nervous system. 5-HT3 receptors appear most promising as targets for novel drugs.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Agonist binding at this receptor results in an inward flux of cations and thus an excitation of the host cell (Yakel and Jackson, 1988). 5-HT3 receptors are thought to be most highly expressed in brainstem (Kilpatrick et al, 1989;Gehlert et al, 1991;Laporte et al, 1992;Parker et al, 1996) but have also been detected in dopaminergic brain regions such as the NA (Kilpatrick et al, 1987;Barnes et al, 1990;Gehlert et al, 1991;Parker et al, 1996;Morales et al, 1998), the PFC (Kilpatrick et al, 1987(Kilpatrick et al, , 1989Barnes et al, 1990;Gehlert et al, 1991;Tecott et al, 1993;Morales et al, 1998), the striatum (Kilpatrick et al, 1987(Kilpatrick et al, ,1989Laporte et al, 1992;Parker et al, 1996;Morales et al, 1998) and the SN (Laporte et al, 1992). It is worth noting that the expression of 5-HT3 receptors in the striatum is low in comparison with the PFC and NA.…”