Linked Life Data

12859343

Source:http://linkedlifedata.com/resource/pubmed/id/12859343

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-7-15
pubmed:abstractText
The cholinergic system is crucial for higher brain functions including learning and memory. These functions are mediated primarily by muscarinic acetylcholine receptors (mAChRs) that consist of five subtypes (M(1)-M(5)). A recent study suggested a novel role of acetylcholine as a potent enhancer of endocannabinoid signalling that acts retrogradely from postsynaptic to presynaptic neurons. In the present study, we further investigated the mechanisms of this cholinergic effect on endocannabinoid signalling. We made paired whole-cell recordings from cultured hippocampal neurons, and monitored inhibitory postsynaptic currents (IPSCs). The postsynaptic depolarization induced a transient suppression of IPSCs (DSI), a phenomenon known to involve retrograde signalling by endocannabinoids. The cholinergic agonist carbachol (CCh) markedly enhanced DSI at 0.01-0.3 microM without changing the presynaptic cannabinoid sensitivity. The facilitating effect of CCh on DSI was mimicked by the muscarinic agonist oxotremorine-M, whereas it was eliminated by the muscarinic antagonist atropine. It was also blocked by a non-hydrolizable analogue of GDP (GDP-beta-S) that was applied intracellularly to postsynaptic neurons. The muscarinic enhancement of DSI persisted to a substantial degree in the neurons prepared from M1-knockout and M3-knockout mice, but was virtually eliminated in the neurons from M1/M3-compound-knockout mice. CCh still enhanced DSI significantly under the blockade of postsynatpic K(+) conductance, and did not significantly influence the depolarization-induced Ca(2+) transients. These results indicate that the activation of postsynaptic M1 and M3 receptors facilitates the depolarization-induced release of endocannabinoids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12859343-Animals, pubmed-meshheading:12859343-Animals, Newborn, pubmed-meshheading:12859343-Calcium Signaling, pubmed-meshheading:12859343-Carbachol, pubmed-meshheading:12859343-Cells, Cultured, pubmed-meshheading:12859343-Electrophysiology, pubmed-meshheading:12859343-Endocannabinoids, pubmed-meshheading:12859343-Excitatory Postsynaptic Potentials, pubmed-meshheading:12859343-Fatty Acids, Unsaturated, pubmed-meshheading:12859343-Gallamine Triethiodide, pubmed-meshheading:12859343-Hippocampus, pubmed-meshheading:12859343-Mice, pubmed-meshheading:12859343-Muscarinic Agonists, pubmed-meshheading:12859343-Mutation, pubmed-meshheading:12859343-Nicotinic Antagonists, pubmed-meshheading:12859343-Parasympathetic Nervous System, pubmed-meshheading:12859343-Patch-Clamp Techniques, pubmed-meshheading:12859343-Potassium Channels, pubmed-meshheading:12859343-Rats, pubmed-meshheading:12859343-Receptor, Muscarinic M1, pubmed-meshheading:12859343-Receptor, Muscarinic M3, pubmed-meshheading:12859343-Receptors, Muscarinic, pubmed-meshheading:12859343-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus.
pubmed:affiliation
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't