A COMPARATIVE AUTORADIOGRAPHIC STUDY OF 5-HT1D BINDING-SITES IN HUMANAND GUINEA-PIG BRAIN USING DIFFERENT RADIOLIGANDS

Quantitative receptor autoradiography was used to examine the 5-hydrox ytryptamine (5-HT, serotonin) binding sites labelled with tonin-5-O-ca rboxymethyl-glycyl-[I-125]tyrosinamide ([I-125]GTI) in human and guine a-pig brain. Competition experiments using 5-carboxamidotryptamine hyd ropyrid-4-yl)pyrrolo[3,2,b]pyrid-5-one(CP93129) and sumatriptan reveal ed monophasic displacement curves in various brain regions, suggesting that a homogeneous population of 5-HT1D binding sites was labelled. D isplacement of [H-3]5-HT (in the presence of 100 nM 8-hydroxy-2(N-dipr opylamino)tetralin (8-OH-DPAT) and 100 nM mesulergine) with unlabelled GTI resulted in monophasic competition curves in substantia nigra, gl obus pallidus and central gray. In contrast, biphasic displacement was observed in hippocampus, nucleus accumbens, claustrum, caudate-putame n and frontal cortex. The distribution of [I-125]GTI sites was compare d to that of [H-3]5-HT binding sites (under so-called '5-HT1D conditio ns', i.e. in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine, in order to block 5-HT1A and 5-HT1C sites, respectively) in human and guinea-pig brain. Qualitative analysis revealed differences in the dis tributions of [I-125]GTI and [H-3]5-HT binding sites. Regions such as CA3 and CA4 of the hippocampus, claustrum and putamen showed [H-3]5-HT binding (under '5-HT1D conditions') but no [I-125]GTI binding sites, indicating that [H-3]5-HT labels besides a GTI sensitive (5-HT1D) rece ptor population, a non-5-HT1A/1B/1C/1D[H-3]5-HT binding site in human and guinea-pig brain. The distribution of these non-5-HT1A/1B/1C/1D[H- 3]5-HT binding sites was studied with [H-3]5-HT under conditions where 5-HT1A, 5-HT1C and 5-HT1D[H-3]5-HT binding sites were saturated by th e presence of 100 nM 8-OH-DPAT, 100 nM mesulergine and 1 mu M GTI. Sig nificant densities of these non-5-HT1A/1B/1C/1D sites were observed in cortical areas, hippocampal structures, nucleus accumbens, amygdala, caudate-putamen and claustrum. It is concluded that [I-125]GTI does no t label the 5-HT1E binding site, since all competition curves obtained with this radioligand were monophasic. By contrast, [H-3]5-HT labels non-5-HT1A/1B/1C/1D[H-3]S-HT binding sites, but it remains to be estab lished whether these sites represent a single receptor population.