Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT

Nature. 1983 Sep;305(5930):140-2. doi: 10.1038/305140a0.

Abstract

Binding studies with appropriate labelled ligands have revealed the existence of two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the central nervous system of mammals. The 5-HT1 type is characterized by a higher affinity for agonists than for antagonists, whereas the 5-HT2 type binds preferentially to antagonists. However, neither of these receptor types apparently corresponds to the presynaptic autoreceptor controlling 5-HT release. In an attempt to identify the presynaptic autoreceptor directly, we synthesized the tritiated derivative of 8-hydroxy-2-(di-n-propylamino) tetralin (PAT), a new tetralin derivative with potent 5-HT agonist properties and carried out binding studies with rat brain membranes. As we report here, in the hippocampus, the properties of 3H-PAT binding sites correspond closely to those of 5-HT1 sites. In contrast, in the striatum, 3H-PAT binding sites exhibit a subcellular distribution and pharmacological characteristics usually associated with presynaptic autoreceptors. Furthermore, a marked loss of 3H-PAT binding sites occurs in the striatum (but not in the hippocampus) after the selective degeneration of serotoninergic fibres in 5,7-hydroxytryptamine (5,7-HT)-treated rats. Conversely, the sprouting of additional 5-HT terminals in the brain stem of adult rats treated at birth with 5,7-HT is associated with an increased density of 3H-PAT binding sites in this region. 3H-PAT thus seems to be a useful ligand for studying the biochemical and pharmacological characteristics of presynaptic autoreceptors in selected regions of rat brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Desipramine / pharmacology
  • Male
  • Naphthalenes / metabolism*
  • Rats
  • Receptors, Serotonin / analysis*
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism
  • Synaptosomes / analysis*
  • Tetrahydronaphthalenes / metabolism*
  • Tissue Distribution

Substances

  • Naphthalenes
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Desipramine