title: Pharmacological and physicochemical properties of pre-versus postsynaptic 5-hydroxytryptamine1A receptor binding sites in the rat brain: a quantitative autoradiographic study.
abstract: Numerous data suggested that the pharmacological and biochemical properties of 5-hydroxytryptamine1A (5-HT1A) receptors exhibit some regional differences in the CNS, notably within the raphe nuclei compared with various forebrain areas (such as the hippocampus). This possibility has been further investigated in the dorsal raphe nucleus and two areas within the hippocampus, the dentate gyrus and the CA1 area, using the quantitative autoradiographic technique. The potencies of 5'-guanylylimidodiphosphate to inhibit the specific binding of 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)tetralin (125I-BH-8-MeO-N-PAT) to 5-HT1A sites and of N-ethylmaleimide to block these sites irreversibly were identical in the dorsal raphe nucleus and the hippocampal areas in rat brain sections. In contrast, slight but significant differences were noted in the pH dependence and pharmacological properties of 5-HT1A sites labeled by 125I-BH-8-MeO-N-PAT in these three regions. Similarly, heat denaturation experiments and tissue exposure to either phospholipase A2 or the alkylating agent 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetraline revealed regional differences in the properties of 5-HT1A sites. However, in most cases, the observed variations were of greater amplitude between the CA1 area and the dentate gyrus, where 5-HT1A sites are located postsynaptically, than between any one of these areas and the dorsal raphe nucleus where they act as (presynaptic) somatodendritic autoreceptors. These data further support that subtypes of 5-HT1A receptors probably exist in the rat brain, but this heterogeneity seems unrelated to the pre- or post-synaptic location of these receptors.
authors.affiliation: Département de Cytologie, CNRS UA 1199, Université Pierre et Marie Curie, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Radja
authors.forename: G
authors.initials: G
authors.lastname: Daval
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: D
authors.initials: D
authors.lastname: Vergé
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013696:Temperature; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C055126:8-methoxy-2-(N-propyl-N-(3'-iodo-4'-hydroxyphenyl)-propionamido-N'-propylamino)tetralin; D006165:Guanylyl Imidodiphosphate; D010741:Phospholipases A; D054467:Phospholipases A2