Kainate Receptors Coupled to G<sub>i</sub>/G<sub>o</sub>Proteins in the  Rat Hippocampus

Cunha, Rodrigo A.; Malva, João O.; Ribeiro, João

doi:10.1124/mol.56.2.429

Cited by 44 publications

(34 citation statements)

References 30 publications

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“…Thus, it is possible that the IGF-II/M6P receptor and PTX-sensitive G-proteins may constitute part of a larger protein complex, and the interaction observed in the present study is mediated indirectly via other protein(s). Although other receptors that lack seven transmembrane domains have also been shown to interact with G-proteins (Cunha et al, 1999;Dalle et al, 2001), our results provide compelling evidence that the single transmembrane domain IGF-II/M6P receptor in the adult rat brain is linked to and can mediate cell signaling by activating a G-protein.…”

Section: Discussionmentioning

confidence: 63%

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Hawkes¹,

Jhamandas²,

Harris³

et al. 2006

J. Neurosci.

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The insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor is a single-pass transmembrane glycoprotein that plays an important role in the intracellular trafficking of lysosomal enzymes and endocytosis-mediated degradation of IGF-II. However, its role in signal transduction after IGF-II binding remains unclear. In the present study, we report that IGF-II/M6P receptor in the rat brain is coupled to a G-protein and that its activation by Leu

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Section: Discussionmentioning

confidence: 63%

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Hawkes¹,

Jhamandas²,

Harris³

et al. 2006

J. Neurosci.

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“…The sensitivity of the KAR-induced depression to pertussis toxin implicates the G i /G o subtype of G-protein in the effect. It is noteworthy that binding studies have suggested a functional coupling between this subclass of G-protein and KARs in hippocampal membranes (Cunha et al, 1999). AMPARs have also been shown to couple to G-proteins (Wang et al, 1997;Kawai and Sterling, 1999).…”

Section: Discussionmentioning

confidence: 99%

Kainate Receptors Depress Excitatory Synaptic Transmission at CA3→CA1 Synapses in the Hippocampus via a Direct Presynaptic Action

Frerking¹,

Schmitz²,

Zhou³

et al. 2001

J. Neurosci.

151

143

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Kainate receptor activation depresses synaptic release of neurotransmitter at a number of synapses in the CNS. The mechanism underlying this depression is controversial, and both ionotropic and metabotropic mechanisms have been suggested. We report here that the AMPA/kainate receptor agonists domoate (DA) and kainate (KA) cause a presynaptic depression of glutamatergic transmission at CA33CA1 synapses in the hippocampus, which is not blocked by the AMPA receptor antagonist GYKI 53655 but is blocked by the AMPA/KA receptor antagonist CNQX. Neither a blockade of interneuronal discharge nor antagonists of several neuromodulators affect the depression, suggesting that it is not the result of indirect excitation and subsequent release of a neuromodulator. Presynaptic depolarization, achieved via increasing extracellular K ϩ , caused a depression of the presynaptic fiber volley and an increase in the frequency of miniature EPSCs. Neither effect was observed with DA, suggesting that DA does not depress transmission via a presynaptic depolarization. However, the effects of DA were abolished by the G-protein inhibitors N-ethylmaleimide and pertussis toxin. These results suggest that KA receptor activation depresses synaptic transmission at this synapse via a direct, presynaptic, metabotropic action. Key words: domoate; kainate; metabotropic; presynaptic; hippocampus; CA1Neurotransmitter receptors in the CNS can be separated into two broad classes: ionotropic receptors, which are coupled to ligandgated conductances, and metabotropic receptors, which couple to GTP-binding proteins. Kainate receptors (KARs) are ionotropic glutamate receptors that, in addition to having conventional postsynaptic actions, are thought to act as presynaptic inhibitors of transmitter release at a number of synapses in the CNS (for review, see Frerking and Nicoll, 2000). The mechanisms underlying this depression are controversial. Both direct actions of presynaptic KARs (Chittajallu et al., 1996;Rodríguez-Moreno et al., 1997;Schmitz et al., 2000) and indirect actions of somatodendritic KARs (Frerking et al., 1999;Chergui et al., 2000;Schmitz et al., 2000) have been proposed to account for this presynaptic effect. The depression has also been suggested to be the downstream result of presynaptic depolarization via the conventional ionotropic actions of KARs (Chittajallu et al., 1996;Kamiya and Ozawa, 1998;Schmitz et al., 2000) or alternatively via a novel KAR-coupled metabotropic cascade (Rodríguez-Moreno and Lerma, 1998;Rodríguez-Moreno et al., 2000).One difficulty in interpreting the effects of KAR activation is the frequent presence of somatodendritic KARs on the presynaptic neurons, which can lead to a number of different types of use-dependent depression. Glutamatergic CA33 CA1 synapses in the hippocampus provide a good system in which to study the KAR-induced depression, because the somatodendritic region of the presynaptic CA3 cells can be removed by microdissection. At these synapses, the KAR agonists kainate (KA) and domoate (DA) both indu...

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“…Direct measurement of presynaptic currents is only possible in exceptionally large nerve terminals [e.g. 48], and even if possible it is sometimes difficult to distinguish ionotropic responses from metabotropic responses tightly coupled to regulation of ion channels [49,50]. Only very few studies have provided convincing evidence, through the use of G protein modifiers, for the involvement of P2Y receptors in modulating neurotransmitter release [51][52][53][54].…”

Section: Problems Found In Defining and Classifying Atp-mediated Presmentioning

confidence: 99%

ATP as a presynaptic modulator

2000

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There is considerable evidence that ATP acts as a fast transmitter or co-transmitter in autonomic and sensory nerves mostly through activation of ionotropic P2X receptors but also through metabotropic P2Y receptors. By analogy, the observations that ATP is released from stimulated central nervous system (CNS) nerve terminals and that responses to exogenously added ATP can be recorded in central neurons, lead to the proposal that ATP might also be a fast transmitter in the CNS. However, in spite of the robust expression of P2 receptor mRNA and binding to P2 receptors in the CNS, the demonstration of central purinergic transmission has mostly remained elusive. We now review evidence to suggest that ATP may also act presynaptically rather than solely postsynaptically in the nervous system.

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Kainate Receptors Coupled to G_i/G_oProteins in the Rat Hippocampus

Cited by 44 publications

References 30 publications

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Kainate Receptors Depress Excitatory Synaptic Transmission at CA3→CA1 Synapses in the Hippocampus via a Direct Presynaptic Action

ATP as a presynaptic modulator

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Kainate Receptors Coupled to Gi/GoProteins in the Rat Hippocampus

Cited by 44 publications

References 30 publications

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

Kainate Receptors Depress Excitatory Synaptic Transmission at CA3→CA1 Synapses in the Hippocampus via a Direct Presynaptic Action

ATP as a presynaptic modulator

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About

Kainate Receptors Coupled to G_i/G_oProteins in the Rat Hippocampus