There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed 'agonist-directed trafficking of receptor stimulus', that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5-HT(2A) and 5-HT(2C) receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP) accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5-HT) differed depending upon whether IP accumulation or AA release was measured. For the 5-HT(2C) receptor system, some agonists (e.g. TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD) favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT(2A) receptor system, all agonists tested had greater relative efficacy for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different for 5-HT(2A) agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist-directed trafficking hypothesis.
|Original language||English (US)|
|Number of pages||7|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - Jan 1 1998|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science