Linked Life Data

11524330

Source:http://linkedlifedata.com/resource/pubmed/id/11524330

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-8-28
pubmed:abstractText
Prostaglandin E(2) receptors, subtype EP(1) (PGE(2)EP(1)) have been linked to several physiologic responses, such as fever, inflammation, and mechanical hyperalgesia. Local anesthetics modulate these responses, which may be due to direct interaction of local anesthetics with PGE(2)EP(1) receptor signaling. We sought to characterize the local anesthetic effects on PGE(2)EP(1) signaling and elucidate mechanisms of anesthetic action. In Xenopus laevis oocytes, recombinant expressed PGE(2)EP(1) receptors were functional (half maximal effect concentration, 2.09 +/- 0.98 x 10(-6) M). Bupivacaine, after incubation for 10 min, inhibited concentration-dependent PGE(2)EP(1) receptor functioning (half-maximal inhibitory effect concentration, 3.06 +/- 1.26 x 10(-6) M). Prolonged incubation in bupivacaine (24 h) inhibited PGE(2)-induced calcium-dependent chloride currents (I(Cl(Ca))) even more. Intracellular pathways were not significantly inhibited after 10 min of incubation in bupivacaine. But I(Cl(Ca)) activated by intracellular injection of GTPgammaS (a nonhydrolyzable guanosine triphosphate [GTP] analog that activates G proteins, irreversible because it cannot be dephosphorylated by the intrinsic GTPase activity of the alpha subunit of the G protein) was reduced after 24 h of incubation in bupivacaine, indicating a G protein-dependent effect. However, inositol 1,4,5-trisphosphate- and CaCl(2)- induced I(Cl(Ca)) were unaffected by bupivacaine at any time points tested. Therefore, bupivacaine's effect is at phospholipase C or at the G protein or the PGE(2)EP(1) receptor. All inhibitory effects were reversible. We conclude that bupivacaine inhibited PGE(2)EP(1) receptor signaling at clinically relevant concentrations. These effects could, at least in part, explain how local anesthetics affect physiologic responses such as fever, inflammation, and hyperalgesia during the perioperative period.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0003-2999
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
628-34
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
The inhibitory effect of bupivacaine on prostaglandin E(2) (EP(1)) receptor functioning: mechanism of action.
pubmed:affiliation
Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Münster, Münster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't