title: [3H]sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study.
abstract: We have used in vitro autoradiography to visualize [3H]sumatriptan binding sites in sections of guinea-pig and rat brain. In saturation studies, this ligand recognized a single saturable population of high affinity binding sites in all regions examined (pKD = 8.3-9.3). While 5-HT and the sumatriptan derivative CP-122,288 (5-methyl-aminosulfonylmethyl-3-(N-methylpyrrolidin-2R-yl-me thyl)- 1 H-indole) competed for [3H]sumatriptan binding sites with a high affinity and monophasic profile, displacement experiments with 5-carboxamidotryptamine revealed the existence of 2 classes of binding sites. The high affinity component (pKD = 9.2-9.9) probably corresponded to 5-HT1B (rat) or 5-HT1D (guinea-pig) receptors. The intermediate affinity (pKD = 5.7-7.3) of the other component, taken together with their high affinity for [3H]sumatriptan, was similar to that of the cloned 5-HT1F receptor. The regional distribution of the 5-HT1B/1D [3H]sumatriptan binding sites was in agreement with previously published studies (striatonigral system, hypothalamus, central gray, superficial layer of the superior colliculus) and corresponded to the pattern of serotonin-5-O-carboxymethyl-glycyl [125I]tyrosinamide labeling in consecutive sections. [3H]sumatriptan binding sites with a low affinity for 5-CT predominated in the intermediate neocortical layers, the claustrum (in the guinea-pig only), the mammillary nuclei, most of the thalamic nuclei and the principal oculomotor nucleus (in the guinea-pig only). This distribution is very similar to that of 5-HT1F mRNA, indicating further the identity of these sites with 5-HT1F receptors. Very high densities of 5-HT1F sites were also found in the rat parafascicular nucleus. Some regions, such as the caudate/nucleus, the lateral geniculate nuclei and the spinal trigeminal nucleus appeared to contain both 5-HT1B/1D and 5-HT1F binding sites. Ketanserin had a low affinity for [3H]sumatriptan binding sites in all guinea-pig brain regions, compatible with the presence of the 5-HT1D beta subtype. An exception was the substantia nigra, where a significant proportion of sites displayed an intermediate affinity for this compound, suggesting the presence of 5-HT1D chi receptors. [3H]5-HT labeled 5-HT1F sites in the claustrum and intermediate cortical layers in the guinea-pig. However these data show that [3H]sumatriptan, in the presence of 10 nM 5-carboxamidotryptamine, is a more suitable radioligand to study the distribution of 5-HT1F binding sites.
authors.affiliation: Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Charlestown 02129, USA.
authors.forename: C
authors.initials: C
authors.lastname: Waeber
authors.forename: M A
authors.initials: MA
authors.lastname: Moskowitz
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D011759:Pyrrolidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D018170:Sumatriptan / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C085263:CP 122288; D018170:Sumatriptan