Identification of 5-HT2 receptors, alpha 1-adrenoceptors and amine release sites in rat brain by autoradiography with [125I]7-amino-8-iodo-ketanserin.
Using autoradiographical techniques, we found that [125I]7-amino-8-iodo-ketanserin ([125I]AMIK) labelled with high affinity 5-HT2 receptors, alpha 1-adrenoceptors and sites involved in the release of biogenic amines and metabolites. The three binding sites for [125I]AMIK were identified by using selective inhibitors, i.e. BW 501 for 5-HT2 receptors, prazosin for alpha 1-adrenoceptors and tetrabenazine for the sites involved in the release of biogenic amines and metabolites. Using quantitative image analysis, we calculated the inhibition curves for the drugs in areas containing one of the receptor binding sites, i.e. the claustrum for 5-HT2 receptors, the thalamic nuclei for the alpha 1-adrenoceptors and the rostral part of the caudate putamen for the release sites. By using appropriate combinations of [125I]AMIK and drugs to occlude other binding sites, we could selectively label 5-HT2 receptors (in the presence of 0.1 microM prazosin and 1 microM tetrabenazine), alpha 1-adrenoceptors (in the presence of 1 microM BW 501 and 1 microM tetrabenazine) and release sites (in the presence 0.1 microM prazosin and 1 microM BW 501). Most binding to 5-HT2 receptors was observed in the cortical areas, the caudal caudate-putamen and the substantia nigra, while moderate binding was noticed in the nucleus accumbens, the olfactory bulb and the olfactory tubercle. There were many alpha 1-adrenoceptors in the numerous thalamic nuclei and few in the cortical areas, the periaqueductal grey matter and the substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)
Schotte
A
A
Janssen Research Foundation, Department of Biochemical Pharmacology, Beerse, Belgium.
Leysen
J E
JE
D000578:Amidines / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007650:Ketanserin / Q000031:analogs & derivatives*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D011985:Receptors, Serotonin / Q000032:analysis*; D012702:Serotonin Antagonists / Q000378:metabolism; D013747:Tetrabenazine / Q000494:pharmacology
D000578:Amidines; D000588:Amines; D007457:Iodine Radioisotopes; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C050315:7-amino-8-iodoketanserin; C029751:BW 501C; D007650:Ketanserin; D011224:Prazosin; D013747:Tetrabenazine