Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of tandospirone (TDS) on dissociated rat dorsal raphe neurones were investigated using the patch-clamp method. 2. Under current-clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of firing rates. 3. Under voltage-clamp conditions, TDS induced an inward rectifying K+ current in a concentration-dependent manner. 4. The TDS-induced K+ currents (I(TDS)) were mimicked by 8-OH-DPAT, a 5-HT1A agonist. The I(TDS) was blocked by spiperone, a 5-HT1A receptor antagonist, in a concentration-dependent manner. 5. N-Ethylmaleimide, an agent which uncouples between the receptor and the G-protein, irreversibly blocked the I(TDS). 6. In neurones perfused intracellularly with a pipette-solution containing GTP using the conventional whole-cell patch recording, the I(TDS) showed a gradual rundown. When the neurones were perfused with GTPgammaS, TDS activated the inwardly rectifying K+ current in an irreversible manner. 7. In the inside-out patch recording mode, TDS-activated single K+ channel currents (i(TDS)) which also showed an inward rectification. When the GDP in cytosolic side was completely replaced with GTP, the open probability of i(TDS) significantly increased. 8. These results indicate that the activation of 5-HT1A receptors by TDS directly opens the inward rectifying K+ channels via a G-protein mediated process.
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PMID:Tandospirone-induced K+ current in acutely dissociated rat dorsal raphe neurones. 969 74

I. 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. Mutagenesis and modeling studies point out that the ligand-binding sites in serotonin receptors are located in the transmembrane domain. However, these binding sites are not very well characterized. Since disulfide bonds and sulfhydryl groups have been shown to play vital roles in the assembly, organization, and function of various G-protein-coupled receptors, we report here the effect of disulfide and sulfhydryl group modifications on the agonist and antagonist binding activity of 5-HT1A receptors from bovine hippocampus. 2. DTT or NEM treatment caused a concentration-dependent reduction in specific binding of the agonist and antagonist in 5-HT1A receptors from bovine hippocampal native and solubilized membranes. This is supported by a concomitant reduction in binding affinity. 3. Pretreatment of the receptor with unlabeled ligands prior to chemical modifications indicate that the majority of disulfides or sulfhydryl groups that undergo modification giving rise to inhibition in binding activity could be at the vicinity of the ligand-binding sites. 4. In addition, ligand-binding studies in presence of GTP-gamma-S, a nonhydrolyzable analogue of GTP, indicate that sulfhydryl groups (and disulfide bonds to a lesser extent) are vital for efficient coupling between the 5-HT1A receptor and the G-protein. 5. Our results point out that disulfide bonds and sulfhydryl groups could play an important role in ligand binding in 5-HT1A receptors.
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PMID:Role of disulfides and sulfhydryl groups in agonist and antagonist binding in serotonin1A receptors from bovine hippocampus. 1110 Sep 75