ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Multiple inhibitory G-protein-coupled receptors resist acute desensitization in the presynaptic but not postsynaptic compartments of neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 46 citations in OpenAlex.
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- Opioid suppression of an excitatory pontomedullary respiratory circuit by convergent mechanisms.eLife · 2023Article
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- Chronic morphine induces adaptations in opioid receptor signaling in a thalamo-cortico-striatal circuit that are projection-dependent, sex-specific and regulated by mu opioid receptor phosphorylation.bioRxiv : the preprint server for biology · 2023Article
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- Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.Frontiers in systems neuroscience · 2022Review
- Cellular Tolerance Induced by Chronic Opioids in the Central Nervous System.Frontiers in systems neuroscience · 2022Review
- Individual arcuate nucleus proopiomelanocortin neurons project to select target sites.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
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- Recent Progress in Opioid Research from an Electrophysiological Perspective.Molecular pharmacology · 2020Review
- Opioid Pharmacology under the Microscope.Molecular pharmacology · 2020Review
- Opioid presynaptic disinhibition of the midbrain periaqueductal grey descending analgesic pathway.British journal of pharmacology · 2020Article
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- Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization.International journal of molecular sciences · 2020Article
- Agonist-dependent development of delta opioid receptor tolerance in the colon.Cellular and molecular life sciences : CMLS · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Acute desensitization is a common property of G(i/o)-coupled receptors. Recent data, however, suggest that, unlike μ-opioid receptors (MORs) located somatodendritically in neurons or expressed in heterologous systems, MORs in the presynaptic compartment of neurons are resistant to acute desensitization. It is not yet clear whether this differential desensitization is a shared property of many G(i/o)-coupled receptors nor whether receptors located presynaptically and postsynaptically in a single cell type display differential desensitization. Here, whole-cell recordings were made from proopiomelanocortin (POMC) neurons in mouse brain slices. Agonists for μ-opioid, nociceptin, and GABA(B) receptors induced postsynaptic currents that desensitized within minutes, whereas inhibition of presynaptic transmitter release mediated by these receptors was maintained throughout agonist exposure. Expression of channelrhodopsin2 in POMC neurons allowed for light-evoked transmitter release from POMC neuron terminals, which was detected by recording postsynaptic currents in downstream neurons. Light-evoked currents were inhibited throughout the application of all agonists tested. Thus, the same receptors that desensitize when expressed in the postsynaptic compartment of POMC neurons resist desensitization when located in the presynaptic compartment. Pharmacologic knockdown of MORs revealed that depletion of receptor reserve does not account for presynaptic resistance to desensitization. In ∼25% of recordings with GABA(B) agonist application, presynaptic GABA(B) receptors desensitized, suggesting that resistance to desensitization is not due to an intrinsic property of the terminals themselves. Together, the results indicate that a variety of presynaptic receptors can continue to function after their postsynaptic counterparts desensitize and suggest that a compartment-specific modification may confer resistance to desensitization.
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Registered trials
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.