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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1996-10-11
pubmed:abstractText
Activation of phospholipase C (PLC) coupled to phosphoinositide (PtdIns) hydrolysis occurs through one of the two pathways. One of the major pathways for the neurotransmitter signaling involves phosphoinositide (PtdIns) specific and G-protein dependent PLC-beta, which stimulates the formation of inositol triphosphate (IP3) and inositol tetraphosphate (IP4). Another pathway through the stimulation of calcium influx can directly activate all of the PLC isozymes. At least three isozymes of PLC have been characterized in the brain; PLC-A (alpha), PLC-I (beta) and PLC-II (gamma), which are shown to be localized differentially in brain regions. Muscarinic-cholinergic signals are mediated in large part through the hydrolysis of PtdIns by PLC. To investigate changes in muscarinic coupling to PLC during aging, we examined carbachol stimulated and calcium stimulated PtdIns hydrolysis in cerebral cortical membranes in young, middle aged and old rats. In order to determine whether PtdIns hydrolysis changes correspond to PLC isozyme expression in these animals, we examined three subtypes of PLC mRNA expression in brain sections of young and old rats using in situ hybridization technique. Our study indicated decreased carbachol-induced PLC activity in the cerebral cortex and, in contrast, increased PLC-beta mRNA in the frontal cortex and superficial cortical layer of aged rats. PLC-alpha mRNA was decreased in hippocampal regions of older rats. These studies suggest that during aging there is an uncoupling of muscarinic stimulated PtdIns hydrolysis, which is accompanied by an increased PLC-beta mRNA and decreased PLC-alpha mRNA that may represent compensatory changes in PLC expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
708
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-52
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8720870-Aging, pubmed-meshheading:8720870-Animals, pubmed-meshheading:8720870-Base Sequence, pubmed-meshheading:8720870-Brain, pubmed-meshheading:8720870-Calcium, pubmed-meshheading:8720870-Carbachol, pubmed-meshheading:8720870-Enzyme Activation, pubmed-meshheading:8720870-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:8720870-In Situ Hybridization, pubmed-meshheading:8720870-Isoenzymes, pubmed-meshheading:8720870-Male, pubmed-meshheading:8720870-Molecular Sequence Data, pubmed-meshheading:8720870-Oligonucleotide Probes, pubmed-meshheading:8720870-Organ Specificity, pubmed-meshheading:8720870-Phosphatidylinositols, pubmed-meshheading:8720870-RNA, Messenger, pubmed-meshheading:8720870-Rats, pubmed-meshheading:8720870-Rats, Inbred F344, pubmed-meshheading:8720870-Receptors, Muscarinic, pubmed-meshheading:8720870-Signal Transduction, pubmed-meshheading:8720870-Transcription, Genetic, pubmed-meshheading:8720870-Type C Phospholipases
pubmed:year
1996
pubmed:articleTitle
Age-related loss of cholinergic-muscarinic coupling to PLC: comparison with changes in brain regional PLC subtypes mRNA distribution.
pubmed:affiliation
Neuropsychiatric Research Institute, Fargo, ND 58103, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't