Modulation of agonist and antagonist interactions in serotonin 1A receptors by alcohols

Harikumar, Kaleeckal G.; Chattopadhyay, Amitabha

doi:10.1016/s0014-5793(98)01284-8

Cited by 23 publications

(9 citation statements)

References 47 publications

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“…The direct effect of various alcohols on ligand binding and G-protein coupling of the bovine hippocampal 5-HT 1A receptor has been examined by Chattopadhyay (1998b, 2000). The results show that alcohols inhibit the specific binding of the agonist 8-OH-DPAT (except in case of ethanol) and the antagonist p-MPPF to 5-HT 1A receptors in a concentration dependent manner (Harikumar and Chattopadhyay, 1998b). These results further show that the action of alcohols on the hippocampal 5-HT 1A receptor could be modulated by guanine nucleotides .…”

Section: Membrane Biology Of Serotonin 1a Receptors: Receptor-cholestmentioning

confidence: 56%

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

2005

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1. Serotonin is an intrinsically fluorescent biogenic amine that acts as a neurotransmitter and is found in a wide variety of sites in the central and peripheral nervous system. Serotonergic signaling appears to play a key role in the generation and modulation of various cognitive and behavioral functions. 2. Serotonin exerts its diverse actions by binding to distinct cell surface receptors which have been classified into many groups. The serotonin1A (5-HT1A) receptor is the most extensively studied of the serotonin receptors and belongs to the large family of seven transmembrane domain G-protein coupled receptors. 3. The tissue and sub-cellular distribution, structural characteristics, signaling of the serotonin1A receptor and its interaction with G-proteins are discussed. 4. The pharmacology of serotonin1A receptors is reviewed in terms of binding of agonists and antagonists and sensitivity of their binding to guanine nucleotides. 5. Membrane biology of 5-HT1A receptors is presented using the bovine hippocampal serotonin1A receptor as a model system. The ligand binding activity and G-protein coupling of the receptor is modulated by membrane cholesterol thereby indicating the requirement of cholesterol in maintaining the receptor organization and function. This, along with the reported detergent resistance characteristics of the receptor, raises important questions on the role of membrane lipids and domains in the function of this receptor.

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Section: Membrane Biology Of Serotonin 1a Receptors: Receptor-cholestmentioning

confidence: 56%

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

2005

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“…It is therefore important to determine the actual concentration of the anesthetics partitioned into the membrane while considering their effects on the ligand-binding properties of the 5-HT 1A receptor. The concentrations of the local anesthetics in membranes can be determined from their membrane/buffer partition coefficients (De Paula and Schreier, 1995) using a formalism previously developed by us (Harikumar and Chattopadhyay, 1998b) to determine partitioning of alcohols into membranes. Calculations by this approach using literature values of the membrane/buffer partition coefficients of tertiary amine local anesthetics (De Paula and Schreier, 1995) showed that most (>99%) of the added anesthetics got partitioned into the membrane due to their high partition coefficient values in the range of concentrations used by us.…”

Section: Discussionmentioning

confidence: 99%

“…The final concentration of ethanol in the assay tubes was maintained at 0.05% (v/v). Control experiments showed that ethanol at this concentration did not affect the ligand-binding properties of the receptor (Harikumar and Chattopadhyay, 1998b). The incubation was terminated by rapid filtration under vacuum in a Millipore multiport filtration apparatus through Whatman GF/B (1.0 µm pore size) 2.5 cm diameter glass microfiber filters which were presoaked in 0.15% polyethylenimine for 3 h (Bruns et al, 1983).…”

Section: Receptor Binding Assays Of Hippocampal Membranes Treated Witmentioning

confidence: 99%

Interaction of Serotonin_1AReceptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics

Kalipatnapu

Chattopadhyay

2004

Cell Mol Neurobiol

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SUMMARY1. We have examined the interaction of tertiary amine local anesthetics with the bovine hippocampal serotonin 1A (5-HT 1A ) receptor, an important member of the G-proteincoupled receptor superfamily.2. The local anesthetics inhibit specific agonist and antagonist binding to the 5-HT 1A receptor at a clinically relevant concentration range of the anesthetics. This is accompanied by a concomitant reduction in the binding affinity of the 5-HT 1A receptor to the agonist. Interestingly, the extent of G-protein coupling of the receptor is reduced in the presence of the local anesthetics.3. Fluorescence polarization measurements using depth-dependent fluorescent probes show that procaine and lidocaine do not show any significant change in membrane fluidity. On the other hand, tetracaine and dibucaine were found to alter fluidity of the membrane as indicated by a fluorescent probe which monitors the headgroup region of the membrane.4. The local anesthetics showed inhibition of agonist binding to the 5-HT 1A receptor in membranes depleted of cholesterol more or less to the same extent as that of control membranes in all cases. This suggests that the inhibition in ligand binding to the 5-HT 1A receptor brought about by local anesthetics is independent of the membrane cholesterol content.5. Our results on the effects of the local anesthetics on the ligand binding and G-protein coupling of the 5-HT 1A receptor support the possibility that G-protein-coupled receptors could be involved in the action of local anesthetics.

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“…In addition, the 5-HT 1A receptor antagonists represent a major class of molecules with potential therapeutic effects in anxiety-or stress-related disorders [30]. We have earlier solubilized and partially purified the 5-HT 1A receptor from bovine hippocampus [31,32] and have shown modulation of ligand binding to the bovine hippocampal 5-HT 1A receptor by metal ions, guanine nucleotides, alcohols, local anesthetics, membrane cholesterol, and covalent modifications of the disulfides and sulfhydryl groups [33][34][35][36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Ligand Binding Characteristics of the Human Serotonin1A Receptor Heterologously Expressed in CHO Cells

et al. 2004

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The serotonin1A (5-HT1A) receptors are important members of the superfamily of seven transmembrane domain G-protein coupled receptors. They appear to be involved in various behavioral, cognitive and developmental functions. Mammalian cells in culture heterologously expressing membrane receptors represent convenient systems to address problems in receptor biology. We report here the pharmacological characterization of one of the first isolated clones of CHO cells stably expressing the human 5-HT1A receptor using the selective agonist 8-OH-DPAT and antagonist p-MPPF. In addition, we demonstrate that agonist and antagonist binding to the receptor exhibit differential sensitivity to the non-hydrolyzable GTP analogue, GTP-gamma-S, as was observed earlier with the native receptor from bovine hippocampus. These results show that the human 5-HT1A receptor expressed in CHO cells displays characteristic features found in the native receptor isolated from bovine hippocampus and promises to be a potentially useful system for future studies of the receptor.

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Modulation of agonist and antagonist interactions in serotonin 1A receptors by alcohols

Cited by 23 publications

References 47 publications

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

Interaction of Serotonin_1AReceptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics

Ligand Binding Characteristics of the Human Serotonin1A Receptor Heterologously Expressed in CHO Cells

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Modulation of agonist and antagonist interactions in serotonin 1A receptors by alcohols

Cited by 23 publications

References 47 publications

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

The Serotonin1A A Receptor: A Representative Member of the Serotonin Receptor Family

Interaction of Serotonin1AReceptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics

Ligand Binding Characteristics of the Human Serotonin1A Receptor Heterologously Expressed in CHO Cells

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Interaction of Serotonin_1AReceptors from Bovine Hippocampus with Tertiary Amine Local Anesthetics