Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At parallel fiber (PF) to Purkinje cell (PC) synapses, depolarization-induced suppression of excitation (DSE) and suppression of PF-excitatory postsynaptic currents (EPSCs) by activation of postsynaptic mGluR1 glutamate (Glu) receptors involve retrograde release of endocannabinoids. However, Levenes et al. suggested instead that Glu was the retrograde messenger in this latter case. Because the study by Levenes et al. was performed in nearly mature rats, whereas most others were performed in juvenile animals, DSE was re-investigated in juvenile versus nearly mature rats and mice. Indeed, DSE was preferred here to agonist-induced suppression of PF-EPSCs, to avoid possible indirect effects in this latter case. In 10- to 12-day-old rats, DSE of PF-EPSCs was entirely mediated through retrograde release of endocannabinoids. In 18- to 22-day-old-rats, DSE was partly resistant to CB1 cannabinoid receptor antagonists. The remaining component was potentiated by the Glu uptake inhibitor d-threo-beta-benzyloxyaspartate (d-TBOA) and blocked by the desensitizing kainate (KA) receptor agonist (2S,4R)-4-methylglutamic acid (SYM 2081). This SYM-2081-sensitive component of DSE was accompanied by a paired-pulse facilitation increase that was also potentiated by d-TBOA and blocked by SYM 2081. In nearly mature wild-type and GluR6 -/- mice, results fully confirmed the presence of an endocannabinoid-independent component of DSE that involves retrograde release of Glu and activation of presynaptic KA receptors including GluR6 receptor subunits. Therefore retrograde release of Glu by PCs participates to DSE at PF-PC synapses in nearly mature rodents but not in juvenile ones, and Glu probably operates through activation of presynaptic KA receptors that include GluR6 receptor subunits.
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PMID:Developmental changes in retrograde messengers involved in depolarization-induced suppression of excitation at parallel fiber-Purkinje cell synapses in rodents. 1710 93

In cerebellar Purkinje cells (PCs), activation of postsynaptic mGluR1 receptors inhibits parallel fiber (PF) to PC synaptic transmission by retrograde signaling. However, results were conflicting with respect to whether endocannabinoids or glutamate (Glu) is the retrograde messenger involved. Experiments in cerebellar slices from 10- to 12-day-old rats and mice confirmed that suppression of PF-excitatory postsynaptic currents (EPSCs) by mGluR1 agonists was entirely blocked by cannabinoid receptor antagonists at this early developmental stage. In contrast, suppression of PF-EPSCs by mGluR1 agonists was only partly blocked by cannabinoid receptor antagonists in 18- to 22-day-old rats, and the remaining suppression was accompanied by an increase in paired-pulse facilitation. This endocannnabinoidindependent suppression of PF-EPSCs was potentiated by the Glu uptake inhibitor D-threo-beta-benzyloxyaspartate (D-TBOA) and blocked by the desensitizing kainate (KA) receptors agonist SYM 2081, by nonsaturating concentrations of 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX) [but not by GYKI 52466 hydrochloride (GYKI)] and by dialyzing PCs with guanosine 5'-[beta-thio]diphosphate (GDP-betaS). An endocannnabinoid-independent suppression of PF-EPSCs was also present in nearly mature wild-type mice but was absent in GluR6(-/-) mice. The endocannnabinoid-independent suppression of PF-EPSCs induced by mGluR1 agonists and the KA-dependent component of depolarization-induced suppression of excitation (DSE) were blocked by ryanodine acting at a presynaptic level. We conclude that retrograde release of Glu by PCs participates in mGluR1 agonist-induced suppression of PF-EPSCs at nearly mature PF-PC synapses and that Glu operates through activation of presynaptic KA receptors located on PFs and prolonged release of calcium from presynaptic internal calcium stores.
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PMID:Developmental changes in agonist-induced retrograde signaling at parallel fiber-Purkinje cell synapses: role of calcium-induced calcium release. 1785 89