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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-1-14
pubmed:abstractText
A pharmacological approach was used to investigate the cellular mechanism and metabotropic glutamate receptor (mGluR) subtypes that mediate stimulation of basal cyclic AMP (cAMP) formation in slices of the neonatal rat hippocampus. (1S,3 R)-1-Aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD), which is an agonist for phosphoinositide-coupled and inhibitory-coupled cAMP-linked mGluRs in cloned and in situ preparations, produced prominent stimulations of basal cAMP levels (five- to 10-fold). However, the agonists 3,5-dihydroxyphenylglycine (DHPG) and (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), which selectively act on phosphoinositide-coupled and inhibitory cAMP-coupled mGluRs, respectively, only weakly increased cAMP levels. When these two mGluR subtype-selective agonists were added in combination, robust increases in cAMP levels, similar to those observed for 1S,3R-ACPD, were found. Stimulations of cAMP content evoked by 1S,3R-ACPD and combined additions of DHPG plus 2R,4R-APDC occurred at concentrations of these agents that directly couple to other mGluR second messenger responses. However, these stimulatory cAMP responses were prevented by the presence of adenosine deaminase and 8-p-sulfophenyltheophylline (an adenosine receptor antagonist), as well as (+)-alpha-methyl-4-carboxyphenylglycine (an mGluR receptor antagonist). Thus, 1S,3R-ACPD-induced increases in cAMP formation in the neonatal rat hippocampus are mediated by a synergistic interaction between mGluRs coupled to phosphoinositide (group 1) and inhibitory cAMP (group 2), which are indirectly expressed by potentiation of cAMP responses to other agonists (in this case, endogenous adenosine).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1981-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
(1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced increases in cyclic AMP formation in the neonatal rat hippocampus are mediated by a synergistic interaction between phosphoinositide- and inhibitory cyclic AMP-coupled mGluRs.
pubmed:affiliation
Central Nervous System Research, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
pubmed:publicationType
Journal Article, In Vitro