Modulation of antagonist binding to serotonin1A receptors from bovine hippocampus by metal ions.
1. The serotonin1A (5-HT1A) receptors are members of a superfamily of seven transmembrane domain receptors that couple to G-proteins. They appear to be involved in various behavioral and cognitive functions. Although specific 5-HT1A agonists have been discovered more than a decade back, the development of selective 5-HT1A antagonists has been achieved only recently. 2. We have examined the modulation of the specific antagonist [3H]p-MPPF binding to 5-HT1A receptors from bovine hippocampal membranes by monovalent and divalent metal ions. Our results show that the antagonist binding to 5-HT1A receptors is inhibited by both monovalent and divalent cations in a concentration-dependent manner. This is accompanied by a concomitant reduction in binding affinity. 3. Our results also show that the specific antagonist p-MPPF binds to all available receptors in the bovine hippocampal membrane irrespective of their state of G-protein coupling and other serotonergic ligands such as 5-HT and OH-DPAT effectively compete with the specific antagonist [3H]p-MPPF. 4. These results are relevant to ongoing analyses of the overall modulation of ligand binding in G-protein-coupled seven transmembrane domain receptors.
Harikumar
K G
KG
Centre for Cellular and Molecular Biology, Hyderabad, India.
Chattopadhyay
A
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000493:pharmacokinetics; D000818:Animals; D002412:Cations / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D010879:Piperazines / Q000493:pharmacokinetics; D011188:Potassium / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000493:pharmacokinetics*; D012964:Sodium / Q000494:pharmacology
D000631:Aminopyridines; D002412:Cations; D008024:Ligands; D008670:Metals; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D008345:Manganese; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine; D012964:Sodium; D008274:Magnesium; D011188:Potassium