Agonist-induced muscarinic cholinergic receptor internalization, recycling and degradation in cultured neuronal cells

Maloteaux, Jean‐Marie; Hermans, Emmanuel

doi:10.1016/0006-2952(94)90439-1

Cited by 40 publications

(29 citation statements)

References 91 publications

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“…Thus, for example, it is well established that prolonged exposure to cholinergic agonists is associated with the internalization and, ultimately, down-regulation (degradation and/or reduced synthesis) of muscarinic receptors, which seem to be the major mediators of cholinergic-driven network desynchronization [16,18,57,62] (in particular M1 receptors [65,83]). Where examined, however, internalization was observed to occur rapidly, with membrane receptor levels plateauing within minutes or at most one to three hours following chronic exposure to muscarinic agonists [84][85][86]. These kinetics seem to be too fast to explain the slow time course of adaptation observed here, a mismatch which also applies to the kinetics of nicotinic receptor desensitization [87].…”

Section: Adaptation To Prolonged Neuromodulation: An Inevitable Returmentioning

confidence: 64%

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

2014

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Background: Prolonged neuromodulatory regimes, such as those critically involved in promoting arousal and suppressing sleep-associated synchronous activity patterns, might be expected to trigger adaptation processes and, consequently, a decline in neuromodulator-driven effects. This possibility, however, has rarely been addressed. Results: Using networks of cultured cortical neurons, acetylcholine microinjections and a novel closed-loop 'synchrony-clamp' system, we found that acetylcholine pulses strongly suppressed network synchrony. Over the course of many hours, however, synchrony invariably reemerged, even when feedback was used to compensate for declining cholinergic efficacy. Network synchrony also reemerged following its initial suppression by noradrenaline, but this did not occlude the suppression of synchrony or its gradual reemergence following subsequent cholinergic input. Importantly, cholinergic efficacy could be restored and preserved over extended time scales by periodically withdrawing cholinergic input. Conclusions: These findings indicate that the capacity of neuromodulators to suppress network synchrony is constrained by slow-acting, reactive processes. A multiplicity of neuromodulators and ultimately neuromodulator withdrawal periods might thus be necessary to cope with an inevitable reemergence of network synchrony.

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Section: Adaptation To Prolonged Neuromodulation: An Inevitable Returmentioning

confidence: 64%

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

2014

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“…Agonist-induced internalization of neuroreceptors that are coupled to G-proteins is a well-documented phenomenon (Maloteaux and Hermans 1994;Sternini et al 2000). This concept has also been demonstrated to be true for D 2 -like dopamine receptors (Barbier et al 1997;Ito et al 1999).…”

Section: Discussionmentioning

confidence: 93%

Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Yokoi

2002

Neuropsychopharmacology

279

147

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“…Endocyto sis-mediated internalization of G-protein-coupled recep tors in response to agonist stimulation is one of the nu merous mechanisms by which cellular responses to ago nists are rapidly attenuated (Feger et aI ., 1994; Grady et aI., 1997;Koenig and Edwardson, 1997). Rapid agonist mediated internalization to endosomal compartment has been documented for numerous G-protein-coupled re ceptors (Maloteaux and Hermans, 1994 ; Faure et aI., 1995; Fonseca et aI., 1995;Mantyh et aI., 1995 Grady et aI., 1993). Rapid internalization of D2 receptors in face of an agonist challenge has been demonstrated in several transfected cells (Barton et aI., 1991; Itokawa et aI., 1996; Barbier et aI., 1997; Ng et aI., 1997 ; Ito et aI., 1999; Iwata et aI., 1999;Vickery and von Zastrow, 1999).…”

Section: Laruellementioning

confidence: 99%

mentioning

confidence: 99%

Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review

Laruelle

2000

J Cereb Blood Flow Metab

912

756

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Summary: Several groups have provided evidence that posi tron emission tomography (PET) and single-photon emission computed tomography (SPECT) neuroreceptor imaging tech niques might be applied to measure acute t1uctuations in do pamine (OA) synaptic concentration in the living human brain. Competition between OA and radioligands for binding to O2 receptor is the principle underlying this approach. This new application of neuroreceptor imaging provides a dynamic mea surement of neurotransmission that is likely to be informative to our understanding of neuropsychiatric conditions. This ar ticle reviews and discusses the body of data supporting the feasibility and potential of this imaging paradigm. Endogenous competition studies performed in rodents, nonhuman primates, and humans are first summarized. After this overview, the va lidity of the model underlying the interpretation of these im aging data is critically assessed. The current reference model is defined as the occupancy model, since changes in radiotracer binding potential (BP) are assumed to be directly caused by changes in occupancy of O2 receptors by OA. Experimental data supporting this model are presented. The evidence that manipulation of OA synaptic levels induces change in the BP of several O2 radiotracers (catecholamines and benzamides) is unequivocal. The fact that these changes in BP are mediated by changes in OA synaptic concentration is well documented. The relationship between the magnitude of BP changes measured with PET or SPECT and the magnitude of changes in OA concentration measured by microdialysis supports the use of these noninvasive techniques to measure changes in neuro transmission. On the other hand, several observations remain unexplained. First, the amphetamine-induced changes in the BP of O2 receptor antagonists [1 2 3IJIBZM and [I I Clraclopride last longer than amphetamine-induced changes in OA extracellular concentration. Second, nonbenzamide O2 receptor antagonists, such as spiperone and pimozide, are not affected by changes in OA release, or are affected in a direction opposite to that pre dicted by the occupancy model. Similar observations are re ported with 0 I radiotracers. These results suggest that the changes in BP following changes in OA concentration might not be fully accounted by a simple occupancy model. Specifi cally, the data are reviewed supporting that agonist-mediated receptor internalization might play an important role in char acterizing receptor-ligand interactions. Finally, it is proposed that a better understanding of the mechanism underlying the effects observed with benzamides is essential to develop this imaging technique to other receptor systems. Key Words: Pos itron emission tomography-Single-photon emission computed tomography-Oopamine-Raclopride-IBZM-Spiperone Internalization.Received August 2S, 1999; final revision received December 3, 1999; accepted December 3, 1999. Supported by the National Institute of Mental Health (K02 MHO I 603-0 1). Address correspondence and reprint requests to Ma...

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Agonist-induced muscarinic cholinergic receptor internalization, recycling and degradation in cultured neuronal cells

Cited by 40 publications

References 91 publications

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony

Dopamine D2 and D3 Receptor Occupancy in Normal Humans Treated with the Antipsychotic Drug Aripiprazole (OPC 14597) A Study Using Positron Emission Tomography and [11C]Raclopride

Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review

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