ArticleBritish journal of pharmacology2012
The 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by morphine.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- Orthosteric and Allosteric Activation of Human 5-HTBiophysical journal · 2020Article
- Agonist- and antagonist-induced up-regulation of surface 5-HT3 A receptors.British journal of pharmacology · 2015Article
- Mutagenic analysis of the intracellular portals of the human 5-HT3A receptor.The Journal of biological chemistry · 2013Article
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- The 5-HT3AB receptor shows an A3B2 stoichiometry at the plasma membrane.Biophysical journal · 2013Article
- The minimum M3-M4 loop length of neurotransmitter-activated pentameric receptors is critical for the structural integrity of cytoplasmic portals.The Journal of biological chemistry · 2013Article
- Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeMorphine is an antagonist at 5-HT(3) A receptors. 5-HT(3) and opioid receptors are expressed in many of the same neuronal pathways where they modulate gut motility, pain and reinforcement. There is increasing interest in the 5-HT3B subunit, which confers altered pharmacology to 5-HT(3) receptors. We investigated the mechanisms of inhibition by morphine of 5-HT(3) receptors and the influence of the 5-HT3B subunit. EXPERIMENTAL APPROACH: 5-HT-evoked currents were recorded from voltage-clamped HEK293 cells expressing human 5-HT3A subunits alone or in combination with 5-HT3B subunits. The affinity of morphine for the orthosteric site of 5-HT(3) A or 5-HT(3) AB receptors was assessed using radioligand binding with the antagonist [(3) H]GR65630. KEY
resultsWhen pre-applied, morphine potently inhibited 5-HT-evoked currents mediated by 5-HT(3) A receptors. The 5-HT3B subunit reduced the potency of morphine fourfold and increased the rates of inhibition and recovery. Inhibition by pre-applied morphine was insurmountable by 5-HT, was voltage-independent and occurred through a site outside the second membrane-spanning domain. When applied simultaneously with 5-HT, morphine caused a lower potency, surmountable inhibition of 5-HT(3) A and 5-HT(3) AB receptors. Morphine also fully displaced [(3) H]GR65630 from 5-HT(3) A and 5-HT(3) AB receptors with similar potency. CONCLUSIONS AND IMPLICATIONS: These findings suggest that morphine has two sites of action, a low-affinity, competitive site and a high-affinity, non-competitive site that is not available when the channel is activated. The affinity of morphine for the latter is reduced by the 5-HT3B subunit. Our results reveal that morphine causes a high-affinity, insurmountable and subunit-dependent inhibition of human 5-HT(3) receptors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.