Modulation of [h]-8-oh-dpat Binding to Rat Brain Membranes by Metal Ions

The binding of [H]-8-OH-DPAT to rat hippocampal and cortical membranes was specific and saturable with Kd = 0.87 ± 0.18 nM and Kd = 2.4 ± 0.9 nM, respectively. Guanine nucleotides decreased the [H]-8-OH-DPAT binding affinity without significant influence on the number of binding sites. The radioligand binding affinity was only slightly affected by the pH in the interval from 6 to 9. The 5-HT1A receptors in cortical membranes were considerably more stable than in hippocampus, indicating that the lipid environment determines the stability of the receptor in these brain regions. All chlorides of monovalent metals studied at concentrations above 30 mM decreased the [H]-8-OH-DPAT binding. A significant increase in 2 nM [H]-8-OH-DPAT binding to hippocampal membranes was found in the presence of millimolar concentrations of MgCl2, CaCl2, BaCl2, MnCl2, CoCl2, and NiCl2, while the radioligand binding to cortical membranes was inhibited. It is proposed that different G proteins are coupled to 5-HT1A receptors in rat hippocampus and cerebral cortex.