title: Selective irreversible blockade of 5-hydroxytryptamine1A and 5-hydroxytryptamine1C receptor binding sites in the rat brain by 8-MeO-2'-chloro-PAT: a quantitative autoradiographic study.
abstract: The possible irreversible blockade of 5-hydroxytryptamine1 receptor subtypes 5-hydroxytryptamine1A, 5-hydroxytryptamine1B/5-hydroxytryptamine1D and 5-hydroxytryptamine1C by the chloramine 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetralin (8-MeO-2'-chloro-PAT) was investigated in rat brain sections by quantitative autoradiography using [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT), [3H]5-hydroxytryptamine, [125I]BH-8-MeO-N-PAT and [125I]cyanopindolol as radio-ligands. A marked reduction (-50% to -75%) of [3H]8-OH-DPAT and [125I]BH-8-MeO-N-PAT specific binding to 5-hydroxytryptamine1A sites in the hippocampus (CA1 area) and the dorsal raphe nucleus, and of [3H]5-hydroxytryptamine specific binding to 5-hydroxytryptamine1C sites in the choroid plexus was found in sections exposed to 1 microM 8-MeO-2'-chloro-PAT and then washed extensively. In contrast the specific binding of [3H]5-hydroxytryptamine to 5-hydroxytryptamine1B/5-hydroxytryptamine1D sites and of [125I]cyanopindolol to 5-hydroxytryptamine1B sites in the substantia nigra and dorsal subiculum remained unaltered by this treatment. Similarly [125I]cyanopindolol binding to beta-adrenergic receptors was not affected by 8-MeO-2'-chloro-PAT. Prior occupancy of 5-hydroxytryptamine1A sites by 10 microM 5-hydroxytryptamine or 8-OH-DPAT, and of 5-hydroxytryptamine1C sites by 10 microM 5-hydroxytryptamine prevented any subsequent blockade by 8-MeO-2'-chloro-PAT. These data indicate that 8-MeO-2'-chloro-PAT should be a useful alkylating agent for achieving selective irreversible blockade of central 5-hydroxytryptamine1A and 5-hydroxytryptamine1C receptors in vivo in the rat.
authors.affiliation: Département de Cytologie, CNRS UA 4199, 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 B
authors.initials: MB
authors.lastname: Emerit
authors.forename: M C
authors.initials: MC
authors.lastname: Gallissot
authors.forename: M
authors.initials: M
authors.lastname: Hamon
authors.forename: D
authors.initials: D
authors.lastname: Vergé
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
chemical_list: D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C044827:8-methoxy-2-(N-2'-chloropropyl-N-propyl)aminotetralin; D015081:2-Naphthylamine