Metal ion and guanine nucleotide modulations of agonist interaction in G-protein-coupled serotonin(1A) receptors from bovine hippocampus

K. G. Harikumar, Amitabha Chattopadhyay

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

1. The serotonin type 1A (5-HT(1A)) receptors are members of a superfamily of seven transmembrane domain receptors that couple to GTP- binding regulatory proteins (Gproteins). We have studied the modulation of agonist binding to 5-HT(1A) receptors from bovine hippocampus by metal ions and guanine nucleotide. 2. Bovine hippocampal membranes containing the 5- HT(1A) receptor were isolated. These membranes exhibited high-affinity binding sites for the specific agonist [3H]OH-DPAT. 3. The agonist binding is inhibited by monovalent cations Na+, K+, and Li+ in a concentration- dependent manner. Divalent cations such as Ca2+, Mg2+, and Mn2+, on the other hand, show more complex behavior and induce enhancement of agonist binding up to a certain concentration. The effect of the metal ions on agonist binding is strongly modulated in the presence of GTP-γ-S, a nonhydrolyzable analogue of GTP, indicating that these receptors are coupled to G-proteins. 4. To gain further insight into the mechanisms of agonist binding to bovine hippocampal 5-HT(1A) receptors under these conditions, the binding affinities and binding sites have been analyzed by Scatchard analysis of saturation binding data. Our results are relevant to ongoing analyses of the overall regulation of receptor activity for G-protein-coupled seven transmembrane domain receptors.

Original languageEnglish (US)
Pages (from-to)535-553
Number of pages19
JournalCellular and molecular neurobiology
Volume18
Issue number5
DOIs
StatePublished - Oct 3 1998

Keywords

  • 5-HT(1A) receptor
  • Bovine hippocampus
  • Guanine nucleotide
  • Metal ions
  • OH-DPAT
  • Scatchard analysis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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