title: [3H]8-OH-DPAT labels a 5-HT site coupled to inhibition of phosphoinositide hydrolysis in the dorsal raphe.
abstract: The present study was undertaken to compare the properties of the [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) binding site in the dorsal raphe nucleus with the hippocampal 5-HT1A receptor. In both tissues inclusion of 1 mM Mg2+ enhanced specific [3H]8-OH-DPAT binding, while 1 mM GTP decreased radioligand binding. [3H]8-OH-DPAT appears to bind to a single population of binding sites in both the hippocampus and the dorsal raphe nucleus, although the K(d) for the radioligand at the dorsal raphe site was five times that observed at the hippocampal 5-HT1A receptor. Similarly, although 5-HT and selective 5-HT1A receptor ligands displayed high affinity for the [3H]8-OH-DPAT binding site in the dorsal raphe nucleus, the affinity at the dorsal raphe site was less than that observed at the hippocampal 5-HT1A receptor. 8-OH-DPAT inhibited forskolin-stimulated adenylyl cyclase activity in the hippocampus, but did not alter enzyme activity in the dorsal raphe nucleus. Conversely, 8-OH-DPAT inhibited the accumulation of [3H]inositol phosphates in the dorsal raphe nucleus, but not in the hippocampus. An inhibition of phosphoinositide hydrolysis in the dorsal raphe nucleus also was found with the putative 5-HT1A receptor selective ligands, flesinoxan and gepirone. However, addition of another putative 5HT1A receptor selective ligand, buspirone, did not alter the generation of [3H]inositol phosphates, but blocked the inhibitory effect of 8-OH-DPAT on phosphoinositide hydrolysis. These studies demonstrate that the 8-OH-DPAT binding site in the dorsal raphe nucleus displays a binding profile which is similar to the hippocampal 5-HT1A receptor, but unlike this 5-HT1A receptor the binding site in the dorsal raphe nucleus is negatively coupled to phosphoinositide turnover.
authors.affiliation: Department of Pharmacology and Toxicology, State University of New York at Buffalo, 14214-3000, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Johnson
authors.forename: D
authors.initials: D
authors.lastname: Fiorella
authors.forename: J C
authors.initials: JC
authors.lastname: Winter
authors.forename: R A
authors.initials: RA
authors.lastname: Rabin
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D010716:Phosphatidylinositols / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism*; D014316:Tritium
chemical_list: D010716:Phosphatidylinositols; D014316:Tritium; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin