Autoradiographic characterisation and localisation of 5-HT1D compared to 5-HT1B binding sites in rat brain

Abstract

The regional distribution and the pharmacology of the binding sites labelled with the novel 5-hydroxytryptamine (serotonin) 5-HT1B/1D selective radioligand serotonin-O-carboxy-methyl-glycyl-[125I]tyrosinamide (abbreviated [125I]GTI for the sake of simplicity) was determined using quantitative autoradiography in rat brain. The distribution of [125I]GTI binding sites was largely comparable to that of [125I]iodocyanopindolol ([125I] ICYP) which labels 5-HT1B binding sites (in the presence of 8-OH-DPAT (8-hydroxy-[2N-dipropylamino]tetralin) and isoprenaline, to prevent binding to 5-HT1A and beta-adrenoceptor binding sites), although a detailed analysis revealed differences. The pharmacology of the [125I]GTI binding sites was analysed using compounds known to display high affinity for and/or distinguish between 5-HT1B and 5-HT1D sites: 5-carboxamidotryptamine (5-CT), sumatriptan, CP 93129 (5-hydroxy-3(4-1,2,5,6-tetrahydropyridyl)-4-azaindole), (-)pindolol, PAPP (4[2-[4-[3-(trifluoromethyl)phenyl]-1- piperazinyl]ethyl]benzeneamine), rauwolscine, and 8-OH-DPAT. The displacement of [125I]GTI by 5-CT was monophasic. By contrast, the selective 5-HT1B compound CP 93129 and (-)pindolol produced biphasic curves showing a majority of high affinity sites in the globus pallidus and the substantia nigra, whereas PAPP and sumatriptan (which are somewhat 5-HT1D selective) produced biphasic curves indicating a minority of high affinity sites in these areas. In addition, by blocking the 5-HT1B sites with 100 nM CP 93129, the remaining population of [125I]GTI binding sites could be studied and was found to have high affinity for PAPP, rauwolscine and 8-OH-DPAT. The pharmacological profile of the major binding component was typical of the 5-HT1B type: 5-CT > CP 93129 > or = (-)pindolol > sumatriptan > or = PAPP > rauwolscine. The profile of the minor component of [125I]GTI binding is best characterised as that of a 5-HT1D site: 5-CT > PAPP > or = sumatriptan > rauwolscine > (-)pindolol > or = CP 93129. The localisation of the non 5-HT1B [125I]GTI binding sites was characterised by blocking the 5-HT1B receptors with 100 nM CP 93129. Low densities of the 5-HT1D recognition sites were found to be present in globus pallidus, ventral pallidum, caudate-putamen, subthalamic nucleus, entopeduncular nucleus, substantia nigra (reticular part), nuclei of the (normal and accessory) optic tract, different nuclei of the geniculate body and frontoparietal cortex, although higher densities of 5-HT1B sites were always observed in the same structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…The 5-HT1Dα receptor is, however, a distinct subtype. 5-HT1Dα receptors have been shown to have a similar distribution in the brain as 5-HT1B receptors, albeit at much lower levels in all regions (Bruinvels et al, 1993(Bruinvels et al, , 1994. To date, 5-HT1Dα receptors have no known role in modulating DA release in the brain.…”

5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats

“…5-HT 1B receptors are mostly found presynaptically, in nerve terminals of serotoninergic neurons (autoreceptors) and non-serotoninergic neurons (heteroreceptors), and they are highly expressed in the basal ganglia, particularly in the terminals of the GABAergic striatal efferent neurons, that is globus pallidus, ventral pallidum, substantia nigra pars reticulata, and entopeduncular nucleus, where their stimulation inhibits GABA release (Bruinvels et al, 1993;Chadha et al, 2000;Sari, 2004). Therefore, the 5-HT 1B receptormediated serotoninergic modulation of methylphenidateinduced locomotor activation demonstrated in the present study most probably involves 5-HT 1B receptors localized in the striatal projecting areas.…”

“…Therefore, the 5-HT 1B receptormediated serotoninergic modulation of methylphenidateinduced locomotor activation demonstrated in the present study most probably involves 5-HT 1B receptors localized in the striatal projecting areas. Albeit with lower density, 5-HT 1B receptors are also localized in the dorsal and ventral striatum (caudate-putamen and NAc) and in the ventral tegmental area (VTA; Bruinvels et al, 1993;Sari, 2004). In the striatum, they are probably localized in GABAergic terminals, but they are also localized in glutamatergic terminals and their stimulation inhibits striatal glutamatergic neurotransmission (Morikawa et al, 2000).…”

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

“…The presence of 5-HT 1D (namely, 5-HT 1Da ) receptor and mRNA in the striatum of rodents, primates and humans has been reported, even if weaker levels of both protein-binding and hybridization signals were observed with respect to the 5-HT 1B (Bruinvels et al, 1993a). Similarly to 5-HT 1B receptors, some authors described a discrepancy in the distribution pattern of 5-HT 1D mRNA and its protein in the striatum, SN and GP of mouse brain and therefore hypothesized a 427 presynaptic localization of 5-HT 1D receptors in the latter two areas (Boschert et al, 1994).…”