5-Hydroxytryptamine and (+)-lysergic acid diethylamide displace [3H]thyrotropin-releasing hormone at its binding sites in the rat limbic forebrain.
Binding of [3H]thyrotropin-releasing hormone (TRH) to its receptors in the rat limbic forebrain was partially displaced by 5-hydroxytryptamine (5-HT, ligand for 5-HT1 receptors) and (+)-lysergic acid diethylamide ((+)-LSD, ligand for 5-HT1 and 5-HT2 receptors) at nanomolar concentrations. Spiperone (ligand for 5-HT2 receptors) displaced [3H]TRH in a dose-dependent manner at micromolar concentrations. These results suggest that some TRH receptors are related to 5-HT1 receptors, probably adjoining them on the membrane. This type of TRH receptor is shown to be among the high-affinity receptors which we reported previously. The significance of the receptor-coexistence is such that TRH facilitates serotonergic transmission by increasing the density of 5-HT1 receptors. This finding seems to support a pharmacological observation of other investigators that TRH potentiates 5-HT-induced hyperactivity in mice, probably by affecting postsynaptic 5-HT receptors.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D008032:Limbic System / Q000378:metabolism*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D012701:Serotonin / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014018:Tissue Distribution
D011956:Receptors, Cell Surface; D018025:Receptors, Thyrotropin-Releasing Hormone; D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; D008238:Lysergic Acid Diethylamide